Researchers have identified the gene changes in whose activity due to stress cause anxiety disorders and depression, as well as metabolic disorders like obesity, type 2 diabetes and arteriosclerosis.
These diseases, linked to stress, are reaching epidemic proportions.
Alon Chen of the Weizmann Institute's Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behaviour but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes...
Friday, April 30, 2010
Obesity epidemic blamed on bacteria
Previous research has shown that intestinal bacteria populations differ between the obese and the lean in humans. A new study using mice shows that increased appetite and insulin resistance can be transferred by intestinal bacteria from one mouse to another. This indicates that the presence of the intestinal bacterial contributes to changes in both appetite and metabolism.
The team at Emory were studying mice with an altered immune system so that they lacked Toll-like receptor 5 (TLR5), a receptor that recognises flagellin, and therefore the presence of bacteria. The TLR5 deficient mice were heavier than their normal counterparts and also consumed more food. They had metabolic changes associated with obesity. When the TLR5 deficient mice were fed a restricted diet, they remained insulin resistant. When given a full-fat diet, they developed diabetes and fatty liver disease. When TLR5 deficient mice were given strong antibiotics, enough to kill most of their intestinal flora, their metabolic abnormalities decreased. Studying the gut flora of TLR5 deficient mice and normal mice showed differing compositions of bacterial families. Previous research has already shown that the components of gut flora can alter the ability of the intestines to extract calories from food...
The team at Emory were studying mice with an altered immune system so that they lacked Toll-like receptor 5 (TLR5), a receptor that recognises flagellin, and therefore the presence of bacteria. The TLR5 deficient mice were heavier than their normal counterparts and also consumed more food. They had metabolic changes associated with obesity. When the TLR5 deficient mice were fed a restricted diet, they remained insulin resistant. When given a full-fat diet, they developed diabetes and fatty liver disease. When TLR5 deficient mice were given strong antibiotics, enough to kill most of their intestinal flora, their metabolic abnormalities decreased. Studying the gut flora of TLR5 deficient mice and normal mice showed differing compositions of bacterial families. Previous research has already shown that the components of gut flora can alter the ability of the intestines to extract calories from food...
Monday, April 26, 2010
Chokeberry Extract Found to Regulate Weight Gain, Blood Glucose, and Inflammation in Rats
Chokeberry bushes have for centuries been residents of eastern deciduous forests where their bright red and dark purple fruits continue to be favorite snacks of local bird species. Native Americans have also traditionally eaten dried chokeberries and prepared teas from parts of the plant, and several domesticated varieties now grace contemporary lawns and gardens from coast to coast. However, the chokeberry (Aronia) is enjoying a new claim-to-fame as a potentially powerful antioxidant, and can now be found for sale in the dietary supplement and "health food" aisles of your local pharmacies and grocery stores.
What makes the humble chokeberry so healthful? Scientists think the answer lies in their unusually high levels of substances called anthocyanins (from the Greek anthos + kyanos meaning dark blue). There are many different anthocyanins in these colorful berries, but they all function as antioxidants -- originally protecting the chokeberry seed from sunshine-induced oxidative stress. And when we eat them, they also appear to protect our bodies from a variety of damaging situations, including exposure to pollution and metabolically-derived free radicals. Indeed, a growing body of scientific literature has shown promising effects of chokeberry consumption on diseases ranging from cancer to obesity. These health-promoting effects may be due to the potent anti-inflammatory properties of anthocyanins, as uncontrolled inflammation is now universally recognized as a common thread in many of our most prevalent and deadly diseases. In addition, certain anthocyanins -- including those found in chokeberry -- have also been shown to improve blood sugar and the function of insulin.
To better understand how chokeberries influence health, Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD studied what happens when prediabetic rats are fed chokeberry extracts for an extended period of time. The results of their research were presented on April 25 at the Experimental Biology 2010 meeting in Anaheim, CA. This presentation is part of the scientific program of the American Society for Nutrition, home of the world's leading nutrition researchers.
The researchers first made 18 male rats "prediabetic" or insulin insensitive by feeding them a fructose-rich diet for 6 weeks. Then they randomized the animals to continue drinking either pure water or water spiked with low or high levels of chokeberry extract (CellBerry®, Integrity Nutraceuticals International). After drinking this water for 6 weeks, the groups were compared in terms of body weight, body fat, blood glucose regulation, and molecular markers for inflammation.
Qin and Anderson found that at the end of the study the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans. And to add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.
Of course, human studies will be needed before scientists can declare whether we derive the same health benefits from the chokeberry...
What makes the humble chokeberry so healthful? Scientists think the answer lies in their unusually high levels of substances called anthocyanins (from the Greek anthos + kyanos meaning dark blue). There are many different anthocyanins in these colorful berries, but they all function as antioxidants -- originally protecting the chokeberry seed from sunshine-induced oxidative stress. And when we eat them, they also appear to protect our bodies from a variety of damaging situations, including exposure to pollution and metabolically-derived free radicals. Indeed, a growing body of scientific literature has shown promising effects of chokeberry consumption on diseases ranging from cancer to obesity. These health-promoting effects may be due to the potent anti-inflammatory properties of anthocyanins, as uncontrolled inflammation is now universally recognized as a common thread in many of our most prevalent and deadly diseases. In addition, certain anthocyanins -- including those found in chokeberry -- have also been shown to improve blood sugar and the function of insulin.
To better understand how chokeberries influence health, Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD studied what happens when prediabetic rats are fed chokeberry extracts for an extended period of time. The results of their research were presented on April 25 at the Experimental Biology 2010 meeting in Anaheim, CA. This presentation is part of the scientific program of the American Society for Nutrition, home of the world's leading nutrition researchers.
The researchers first made 18 male rats "prediabetic" or insulin insensitive by feeding them a fructose-rich diet for 6 weeks. Then they randomized the animals to continue drinking either pure water or water spiked with low or high levels of chokeberry extract (CellBerry®, Integrity Nutraceuticals International). After drinking this water for 6 weeks, the groups were compared in terms of body weight, body fat, blood glucose regulation, and molecular markers for inflammation.
Qin and Anderson found that at the end of the study the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans. And to add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.
Of course, human studies will be needed before scientists can declare whether we derive the same health benefits from the chokeberry...
Saturday, April 24, 2010
Genetics in the Gut
Outnumbering our human cells by about 10 to one, the many minuscule microbes that live in and on our bodies are a big part of crucial everyday functions. The lion’s share live in the intestinal tract, where they help to fend off bad bacteria and aid in digestion. But as scientists determine what microbes are actually present and what they are doing, they are discovering that the bugs play an even larger role in human health than previously suspected—and perhaps at times exerting more influence than genes themselves.
A team that included Junjie Qin and Jun Wang of BGI-Shenzhen (formerly the Beijing Genomics Institute) completed a catalogue of some 3.3 million human gut microbe genes. The work, published in the March 4 Nature, adds to the expanding—but nowhere near complete—census of intestinal species. (Scientific American is part of Nature Publishing Group.)
The 3.3 million genes were a good deal “more than what we originally expected,” Wang says. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals the scientists sampled in Denmark and Spain. The team sequenced 576 billion base pairs, much larger than past work that found three billion base pairs. “These bacteria have functions that are essential to our health: they synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system,” Wang points out.
Another group, led by Andrew Gewirtz of Emory University, turned its attention to a particular host gene that seems to affect these intestinal inhabitants. It found that in mice, a loss of one key gene led to a shift in microbiota communities and a rise in insulin resistance, obesity and other symptoms of so-called metabolic syndrome (a cluster of these conditions).
Gewirtz and his co-workers studied mice bred with the genetic deficiency: an absence of Toll-like receptor 5, or TLR5, which has a hand in immune response. They wanted to see how it might change microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. “Obesity is associated with insulin resistance and type 2 diabetes,” Gewirtz says. But “which comes first is not entirely clear.”
As the researchers described in their paper published online March 4 by Science, they found that mice without the TLR5 gene—even when put on restricted diets—still showed insulin resistance, suggesting that the condition might lead to obesity rather than the other way around. But if these mice were allowed to eat as they pleased, they consumed 10 percent more than their peers and, by 20 weeks old, had body mass indexes that were 20 percent higher...
A team that included Junjie Qin and Jun Wang of BGI-Shenzhen (formerly the Beijing Genomics Institute) completed a catalogue of some 3.3 million human gut microbe genes. The work, published in the March 4 Nature, adds to the expanding—but nowhere near complete—census of intestinal species. (Scientific American is part of Nature Publishing Group.)
The 3.3 million genes were a good deal “more than what we originally expected,” Wang says. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals the scientists sampled in Denmark and Spain. The team sequenced 576 billion base pairs, much larger than past work that found three billion base pairs. “These bacteria have functions that are essential to our health: they synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system,” Wang points out.
Another group, led by Andrew Gewirtz of Emory University, turned its attention to a particular host gene that seems to affect these intestinal inhabitants. It found that in mice, a loss of one key gene led to a shift in microbiota communities and a rise in insulin resistance, obesity and other symptoms of so-called metabolic syndrome (a cluster of these conditions).
Gewirtz and his co-workers studied mice bred with the genetic deficiency: an absence of Toll-like receptor 5, or TLR5, which has a hand in immune response. They wanted to see how it might change microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. “Obesity is associated with insulin resistance and type 2 diabetes,” Gewirtz says. But “which comes first is not entirely clear.”
As the researchers described in their paper published online March 4 by Science, they found that mice without the TLR5 gene—even when put on restricted diets—still showed insulin resistance, suggesting that the condition might lead to obesity rather than the other way around. But if these mice were allowed to eat as they pleased, they consumed 10 percent more than their peers and, by 20 weeks old, had body mass indexes that were 20 percent higher...
Gene linking stress to obesity, diabetes discovered
Changes in the activity of a single gene in the brain can lead to metabolic changes that cause mice to develop symptoms associated with type 2 diabetes, as well as trigger anxious behavior.
These findings, discovered by Weizmann Institute of Science researchers, were published online this week in the Proceedings of the National Academy of Sciences (PNAS).
The constant stress many are exposed to in our modern society may thus be taking a heavy toll: Anxiety disorders and depression, as well as metabolic disorders such as obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress.
These problems are reaching epidemic proportions. Type 2 diabetes alone is expected to affect some 360 million people around the world in 20 years.
The connection between stress, changes in appetite and anxiety-related behavior was recently proven scientifically, but the exact reasons for this were not clear until Dr. Alon Chen of the Rehovot institute’s neurobiology department and colleagues made their gene discovery.
They found that all the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes in the metabolism of various substances and even changes in food preferences.
The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved in tying all of these together. Produced in certain brain cells – especially in times of stress – it is known to play a role in regulating the body’s stress response.
These nerve cells have extensions that act as “highways” to speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions – oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including anxiety levels...
These findings, discovered by Weizmann Institute of Science researchers, were published online this week in the Proceedings of the National Academy of Sciences (PNAS).
The constant stress many are exposed to in our modern society may thus be taking a heavy toll: Anxiety disorders and depression, as well as metabolic disorders such as obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress.
These problems are reaching epidemic proportions. Type 2 diabetes alone is expected to affect some 360 million people around the world in 20 years.
The connection between stress, changes in appetite and anxiety-related behavior was recently proven scientifically, but the exact reasons for this were not clear until Dr. Alon Chen of the Rehovot institute’s neurobiology department and colleagues made their gene discovery.
They found that all the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes in the metabolism of various substances and even changes in food preferences.
The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved in tying all of these together. Produced in certain brain cells – especially in times of stress – it is known to play a role in regulating the body’s stress response.
These nerve cells have extensions that act as “highways” to speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions – oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including anxiety levels...
Sunday, April 18, 2010
Mice With High-Altitude Metabolism Stay Slim And Healthy On A High-Fat Diet
Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found.
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said...
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said...
Thursday, April 15, 2010
High-Altitude Metabolism Lets Mice Stay Slim and Healthy on a High-Fat Diet
Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found.
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said.
Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.
"We expected them to die as embryos," said Na Zhang, a graduate student in Johnson's lab and lead author of the study. "Then we saw they can survive for a long time."
"From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy," Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.
"We fed the mice with a very high fat diet -- 60 percent fat -- just to see how they would respond," Zhang said. "Mutants can eat a lot, but they didn't gain a lot of weight. They are less fatty around their middles compared with their littermates."
Obese people develop a "fatty liver," and so did the wild type littermates. The fat mice also developed high blood cholesterol with elevated levels of the "bad" type, LDL. In lean mutants, LDL increased much less.
"All of these observations support that the modified mice have better metabolic profiles," Zhang said...
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said.
Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.
"We expected them to die as embryos," said Na Zhang, a graduate student in Johnson's lab and lead author of the study. "Then we saw they can survive for a long time."
"From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy," Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.
"We fed the mice with a very high fat diet -- 60 percent fat -- just to see how they would respond," Zhang said. "Mutants can eat a lot, but they didn't gain a lot of weight. They are less fatty around their middles compared with their littermates."
Obese people develop a "fatty liver," and so did the wild type littermates. The fat mice also developed high blood cholesterol with elevated levels of the "bad" type, LDL. In lean mutants, LDL increased much less.
"All of these observations support that the modified mice have better metabolic profiles," Zhang said...
Wednesday, April 14, 2010
Brent Batten: Jackson Lab a meeting of mice and men
Move over Mickey.
There’s a new mouse in town. Or at least there will be if Jackson Laboratory can secure the money it’s seeking to build a research facility in Florida.
Mickey’s been the state’s main mouse since 1971 when Walt Disney World opened in Orlando but the Jackson Lab brings with it not only a reputation for doing cutting edge genetic research but also one as the world’s foremost breeder of mice. Or, more accurately, it brings a reputation for doing cutting edge genetic research because it is the world’s foremost breeder of mice.
The Florida facility, planned for eastern Collier County providing the right combination of state, local and private funding can be found, would mainly use computers and not be as mouse-intensive as Jackson’s Bar Harbor, Maine, headquarters, but the work done here would build on nearly a century of experience with the rodent.
Jackson Lab founder C.C. Little in 1929 had a vision for researching the genetic aspects of cancer. At the time, the genetic study of mice had been underway for about 30 years. Little is credited with conceiving of and creating the first inbred strain of laboratory mice to unravel the genetics of cancer.
Today, Jackson Labs maintains about 5,000 different strains of inbred mice. They are used both for research in the lab and for sale to scientists around the world. Do you need an obese mouse with a strong immunity to pancreatic cancer? Jackson can hook you up. A diabetic mouse with lymphoma? Got it. Or, if they don’t, they’ll try to create it for you.
Last year Jackson sold, on a nonprofit basis, about 2.5 million mice to 16,000 labs in 53 countries, according to Joyce Peterson, communications manager for the laboratory. Sixteen Jackson Lab mice are in orbit right now, ferried to the International Space Station by Discovery for an experiment on the effects of space on the immune system.
At any given time there might be 750,000 mice at the Bar Harbor campus. For-profit labs also breed and sell mice but they tend to stock only a few dozen strains, those that are most popular, Peterson said.
“The 20,000 genes that make up humans and mice are pretty much the same,” said Rich Woychik, president of Jackson Labs. “Mice develop the same types of cancer humans develop. We can basically study these things with the mouse.”
Woychik said Florida has been very welcoming to bio-tech companies, an attitude that led Jackson to choose it over offers from places like Boston and Salt Lake City. The work of the Collier County Economic Development Council further steered the lab toward Southwest Florida. “There’s been tremendous enthusiasm in the state for major biomedical investment. Those investments are beginning to pay off,” Woychik said, adding of Collier County, “We really like your community.”
These days, researchers can manipulate the genes of mice to get the combinations they want. “We can essentially swap out genes and exchange them at will,” Woychik said.
But for decades the work was more laborious. Identical mice would be bred, and researchers would look carefully for differences _ mutations _ in their offspring. That sort of work is still done, Peterson said. Mutants are separated and checked every two weeks as scientists look for traits that might make them useful in studying a particular disease. A heavy mouse might come in handy in the study of obesity or diabetes, for instance.
There’s a new mouse in town. Or at least there will be if Jackson Laboratory can secure the money it’s seeking to build a research facility in Florida.
Mickey’s been the state’s main mouse since 1971 when Walt Disney World opened in Orlando but the Jackson Lab brings with it not only a reputation for doing cutting edge genetic research but also one as the world’s foremost breeder of mice. Or, more accurately, it brings a reputation for doing cutting edge genetic research because it is the world’s foremost breeder of mice.
The Florida facility, planned for eastern Collier County providing the right combination of state, local and private funding can be found, would mainly use computers and not be as mouse-intensive as Jackson’s Bar Harbor, Maine, headquarters, but the work done here would build on nearly a century of experience with the rodent.
Jackson Lab founder C.C. Little in 1929 had a vision for researching the genetic aspects of cancer. At the time, the genetic study of mice had been underway for about 30 years. Little is credited with conceiving of and creating the first inbred strain of laboratory mice to unravel the genetics of cancer.
Today, Jackson Labs maintains about 5,000 different strains of inbred mice. They are used both for research in the lab and for sale to scientists around the world. Do you need an obese mouse with a strong immunity to pancreatic cancer? Jackson can hook you up. A diabetic mouse with lymphoma? Got it. Or, if they don’t, they’ll try to create it for you.
Last year Jackson sold, on a nonprofit basis, about 2.5 million mice to 16,000 labs in 53 countries, according to Joyce Peterson, communications manager for the laboratory. Sixteen Jackson Lab mice are in orbit right now, ferried to the International Space Station by Discovery for an experiment on the effects of space on the immune system.
At any given time there might be 750,000 mice at the Bar Harbor campus. For-profit labs also breed and sell mice but they tend to stock only a few dozen strains, those that are most popular, Peterson said.
“The 20,000 genes that make up humans and mice are pretty much the same,” said Rich Woychik, president of Jackson Labs. “Mice develop the same types of cancer humans develop. We can basically study these things with the mouse.”
Woychik said Florida has been very welcoming to bio-tech companies, an attitude that led Jackson to choose it over offers from places like Boston and Salt Lake City. The work of the Collier County Economic Development Council further steered the lab toward Southwest Florida. “There’s been tremendous enthusiasm in the state for major biomedical investment. Those investments are beginning to pay off,” Woychik said, adding of Collier County, “We really like your community.”
These days, researchers can manipulate the genes of mice to get the combinations they want. “We can essentially swap out genes and exchange them at will,” Woychik said.
But for decades the work was more laborious. Identical mice would be bred, and researchers would look carefully for differences _ mutations _ in their offspring. That sort of work is still done, Peterson said. Mutants are separated and checked every two weeks as scientists look for traits that might make them useful in studying a particular disease. A heavy mouse might come in handy in the study of obesity or diabetes, for instance.
A New Way to Lose Weight?
In the quest to fight obesity, scientists are looking at an intriguing question: Is it possible for adults to lose weight by having more baby fat?
Babies have lots of brown adipose tissue, or brown fat, so called because of its color. It is critical to the body's heat production. Unlike white fat cells, which store energy from the food we eat, brown fat consumes calories to generate heat. Revving up this process, research has shown, may help us grow leaner by burning more of the white fat.
Until recently, experts believed that only babies and children had brown fat, to help keep them warm before their young bodies develop techniques like shivering to help them cope with cold temperatures. A discovery last year that adults still have at least some brown fat has spawned hope among scientists and drug developers that the calorie-burning tissue may provide one solution to curbing obesity.
Researchers at Harvard Medical School have identified a protein in the body that appears to spur production of brown fat, including by converting some white fat cells into brown ones, and are now working to develop a drug that would encourage that process. They expect their work could lead to a new approach to treating obesity within a few years.
Other researchers are seeking ways to prompt the brown fat we already have to become more active, thereby prompting our bodies to generate more heat and consume more calories. One technique being investigated: exposing people to colder temperatures, which appears to trigger brown fat to turn up the body's heat.
"The obesity problem continues to be a real time bomb in the United States and in many other countries in the world," says Bruce Spiegelman, a professor of cell biology and medicine at Harvard's Dana-Farber Cancer Center in Boston. "We're not trying to replace diet and exercise, but frequently they're not enough or not effective."
Dr. Spiegelman and his team in 2007 discovered a protein called PRDM16 that appears to regulate the production of brown fat. Mice without PRDM16 don't form good, working brown fat cells, while those with PRDM16 do, studies showed. The researchers then genetically altered some mice so that they would produce greater amounts of PRDM16. The mice's heat generation and calorie-burning rate went up, too, according to research they published in the journal Nature in 2008...
Babies have lots of brown adipose tissue, or brown fat, so called because of its color. It is critical to the body's heat production. Unlike white fat cells, which store energy from the food we eat, brown fat consumes calories to generate heat. Revving up this process, research has shown, may help us grow leaner by burning more of the white fat.
Until recently, experts believed that only babies and children had brown fat, to help keep them warm before their young bodies develop techniques like shivering to help them cope with cold temperatures. A discovery last year that adults still have at least some brown fat has spawned hope among scientists and drug developers that the calorie-burning tissue may provide one solution to curbing obesity.
Researchers at Harvard Medical School have identified a protein in the body that appears to spur production of brown fat, including by converting some white fat cells into brown ones, and are now working to develop a drug that would encourage that process. They expect their work could lead to a new approach to treating obesity within a few years.
Other researchers are seeking ways to prompt the brown fat we already have to become more active, thereby prompting our bodies to generate more heat and consume more calories. One technique being investigated: exposing people to colder temperatures, which appears to trigger brown fat to turn up the body's heat.
"The obesity problem continues to be a real time bomb in the United States and in many other countries in the world," says Bruce Spiegelman, a professor of cell biology and medicine at Harvard's Dana-Farber Cancer Center in Boston. "We're not trying to replace diet and exercise, but frequently they're not enough or not effective."
Dr. Spiegelman and his team in 2007 discovered a protein called PRDM16 that appears to regulate the production of brown fat. Mice without PRDM16 don't form good, working brown fat cells, while those with PRDM16 do, studies showed. The researchers then genetically altered some mice so that they would produce greater amounts of PRDM16. The mice's heat generation and calorie-burning rate went up, too, according to research they published in the journal Nature in 2008...
A New Take on Obesity's Origins
Here's a word that could rock your world: epigenetics.
No, that's not the latest cosmetic treatment for wrinkles, or a cool new weight loss technique — although it does have to do with body weight.
"Epigenetics" means "on or above genetics." And when what's called an "epigenetics mechanism" is at work in a living organism, the genes themselves aren't altered, but how the genes function during the organism's early growth is changed.
This is starting to sound too much like a science class, so let's back up a bit and put this in more human terms.
You're probably aware that when women are pregnant, they often hear from their doctors the mantra, "Don't gain too much weight during your pregnancy." What constitutes "too much" has probably changed over the years, but doctors don't find that old "eating for two" excuse as cute as the rest of us might. In fact, doctors are also advising women who want to become pregnant to get to a healthy weight before doing so.
This isn't just the typical medical "tut-tut-ing," as it turns out. Studies funded by the Agricultural Research Service (ARS) are giving us a new and somewhat startling look at how influences that occur in the womb and perhaps during the first few months of life could affect development of a child's ability to regulate his or her weight, even into adulthood.
Yes, you read that right: If a woman packs on too many pounds during pregnancy, the child's body-weight-regulating mechanism could be harmed by the mom's excess weight. This, in turn, could increase the risk that the child would become an overweight or obese adult, with a higher risk of health problems such as type 2 diabetes or cardiovascular disease.
In the ARS-funded study, scientists looked at weight gains among rat pups whose mothers, called "dams," were either lean or overweight (as a result of deliberate overfeeding in the laboratory) at the time of conception and during pregnancy.
For this study, the scientists mated the lean or overweight female rats with lean males. The pups were nursed only by normal-weight dams to make sure the pups' exposure to their mothers' obesity occurred only in the womb.
All of the rat pups were at a normal weight at birth and at weaning. But when the weaned offspring were given free access to a high-fat ration, the offspring born to overweight mothers gained significantly more weight, and more of that weight as fat, compared to the offspring of the lean mothers. And that's despite the fact that the offspring of the overweight mothers didn't eat any more of the high-fat food than did the pups born to the lean mothers!
What does this mean in real-world terms? The study's results strongly suggest that exposure to the mother's obesity — while in the womb — results in programming of the baby's body-weight-control mechanisms. The factor of the mother's obesity all by itself was enough to significantly increase the baby rats' susceptibility to obesity.
You might be thinking, "Well, maybe those rats were genetically different from each other, so that's why this happened." But the scientists were careful to use only rats that were genetically similar, so that rules out the possibility that genetic differences among the mothers could contribute to the remarkable difference in the baby rats' sensitivity to those high-fat rations.
If this all translates to humans, this study's findings underscore the need for women who want to become pregnant to make sure they're at a healthy weight at conception, and to gain no more than the recommended amount of weight during the pregnancy. Unfortunately, the incidence of obesity or overweight among pregnant women in the United States is on the rise.
What's more, an epigenetics study from 2008 with a population of genetically similar lab mice with a tendency toward obesity showed a "transgenerational amplification of obesity." That means that the overweight mouse mothers gave birth to even heavier baby mice, the females of which gave birth to still heavier baby mice — and on unto the third generation...
No, that's not the latest cosmetic treatment for wrinkles, or a cool new weight loss technique — although it does have to do with body weight.
"Epigenetics" means "on or above genetics." And when what's called an "epigenetics mechanism" is at work in a living organism, the genes themselves aren't altered, but how the genes function during the organism's early growth is changed.
This is starting to sound too much like a science class, so let's back up a bit and put this in more human terms.
You're probably aware that when women are pregnant, they often hear from their doctors the mantra, "Don't gain too much weight during your pregnancy." What constitutes "too much" has probably changed over the years, but doctors don't find that old "eating for two" excuse as cute as the rest of us might. In fact, doctors are also advising women who want to become pregnant to get to a healthy weight before doing so.
This isn't just the typical medical "tut-tut-ing," as it turns out. Studies funded by the Agricultural Research Service (ARS) are giving us a new and somewhat startling look at how influences that occur in the womb and perhaps during the first few months of life could affect development of a child's ability to regulate his or her weight, even into adulthood.
Yes, you read that right: If a woman packs on too many pounds during pregnancy, the child's body-weight-regulating mechanism could be harmed by the mom's excess weight. This, in turn, could increase the risk that the child would become an overweight or obese adult, with a higher risk of health problems such as type 2 diabetes or cardiovascular disease.
In the ARS-funded study, scientists looked at weight gains among rat pups whose mothers, called "dams," were either lean or overweight (as a result of deliberate overfeeding in the laboratory) at the time of conception and during pregnancy.
For this study, the scientists mated the lean or overweight female rats with lean males. The pups were nursed only by normal-weight dams to make sure the pups' exposure to their mothers' obesity occurred only in the womb.
All of the rat pups were at a normal weight at birth and at weaning. But when the weaned offspring were given free access to a high-fat ration, the offspring born to overweight mothers gained significantly more weight, and more of that weight as fat, compared to the offspring of the lean mothers. And that's despite the fact that the offspring of the overweight mothers didn't eat any more of the high-fat food than did the pups born to the lean mothers!
What does this mean in real-world terms? The study's results strongly suggest that exposure to the mother's obesity — while in the womb — results in programming of the baby's body-weight-control mechanisms. The factor of the mother's obesity all by itself was enough to significantly increase the baby rats' susceptibility to obesity.
You might be thinking, "Well, maybe those rats were genetically different from each other, so that's why this happened." But the scientists were careful to use only rats that were genetically similar, so that rules out the possibility that genetic differences among the mothers could contribute to the remarkable difference in the baby rats' sensitivity to those high-fat rations.
If this all translates to humans, this study's findings underscore the need for women who want to become pregnant to make sure they're at a healthy weight at conception, and to gain no more than the recommended amount of weight during the pregnancy. Unfortunately, the incidence of obesity or overweight among pregnant women in the United States is on the rise.
What's more, an epigenetics study from 2008 with a population of genetically similar lab mice with a tendency toward obesity showed a "transgenerational amplification of obesity." That means that the overweight mouse mothers gave birth to even heavier baby mice, the females of which gave birth to still heavier baby mice — and on unto the third generation...
Wednesday, April 07, 2010
Experts to design molecule to shut down fat gene
Scientists in China may have discovered how a gene responsible for obesity kicks into action and want to design a molecule to shut it down.
The fat mass and obesity-associated gene (FTO) sits on human chromosome 16, and several studies in the past have shown it is strongly linked to weight gain. But scientists are just beginning to figure out how the gene actually works.
"This gene was identified through studies done among different ethnic groups -- Caucasions, Chinese, Japanese and (South) Koreans. It has been established that FTO is associated with obesity," Jijie Chai at the National Institute of Biological Sciences in Beijing told Reuters by telephone.
"We believe that FTO is a good target for treatment of obesity. If we can get an active inhibitor (to shut down the FTO gene), we can work toward some sort of therapy."
In a paper published in the latest issue of Nature, lead researcher Chai and his colleagues described how their study found the FTO gene was only activated when it binds to what are known as "single-stranded DNA".
"It has only activity toward single-stranded DNA and has no activity toward double-stranded DNA," Chai said.
"We want to design a small molecule to block FTO activity, to shut down its function. We can feed this (molecule) to mice and see what happens. If the mice get leaner, that would be very exciting," Chai said, but he added that any therapy for obesity would be years away...
The fat mass and obesity-associated gene (FTO) sits on human chromosome 16, and several studies in the past have shown it is strongly linked to weight gain. But scientists are just beginning to figure out how the gene actually works.
"This gene was identified through studies done among different ethnic groups -- Caucasions, Chinese, Japanese and (South) Koreans. It has been established that FTO is associated with obesity," Jijie Chai at the National Institute of Biological Sciences in Beijing told Reuters by telephone.
"We believe that FTO is a good target for treatment of obesity. If we can get an active inhibitor (to shut down the FTO gene), we can work toward some sort of therapy."
In a paper published in the latest issue of Nature, lead researcher Chai and his colleagues described how their study found the FTO gene was only activated when it binds to what are known as "single-stranded DNA".
"It has only activity toward single-stranded DNA and has no activity toward double-stranded DNA," Chai said.
"We want to design a small molecule to block FTO activity, to shut down its function. We can feed this (molecule) to mice and see what happens. If the mice get leaner, that would be very exciting," Chai said, but he added that any therapy for obesity would be years away...
UT Southwestern scientists unravel brain-hormone circuit that helps police diabetes, female fertility
New findings by UT Southwestern Medical Center researchers suggest that the hormones leptin and insulin work together in specific neurons in the hypothalamus region of the brain to affect both the regulation of blood sugar levels in the body and, surprisingly, female fertility.
"Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, which appears online and in the current issue of Cell Metabolism. "Our findings indicate that is not necessarily the case, at least in mice...
"Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, which appears online and in the current issue of Cell Metabolism. "Our findings indicate that is not necessarily the case, at least in mice...
Friday, April 02, 2010
Revolutionary capsule offers hope to diabetics
London: A revolutionary technique that has been found to successfully treat the symptoms of gout could result in a new form of therapy for a range of other medical conditions - such as diabetes and obesity, say experts.
Gout is caused by a build up of uric acid in the bloodstream, which results in crystals of uric acid being deposited in the kidneys and joints, leading to bouts of extreme pain.
Professor Martin Fussenegger of the Swiss Federal Institute of Technology in Zurich designed a 'molecular prosthesis' to treat gout, which is made from human cells designed to detect an increase in levels of uric acid and to respond by secreting an enzyme called urate oxydase, which destroys uric acid.
The treatment consists of implanting a small plastic capsule under the skin, which is loaded with genetically engineered cells taken from the patients themselves.
The capsule effectively works as a synthetic organ balancing the body's chemicals and hormones.
"We have constructed a synthetic genetic circuitry that can detect uric acid in the bloodstream and process this information to produce a therapeutic response," the Independent quoted Fussenegger as saying.
Tests on laboratory mice have proved the efficacy of the new technique...
Gout is caused by a build up of uric acid in the bloodstream, which results in crystals of uric acid being deposited in the kidneys and joints, leading to bouts of extreme pain.
Professor Martin Fussenegger of the Swiss Federal Institute of Technology in Zurich designed a 'molecular prosthesis' to treat gout, which is made from human cells designed to detect an increase in levels of uric acid and to respond by secreting an enzyme called urate oxydase, which destroys uric acid.
The treatment consists of implanting a small plastic capsule under the skin, which is loaded with genetically engineered cells taken from the patients themselves.
The capsule effectively works as a synthetic organ balancing the body's chemicals and hormones.
"We have constructed a synthetic genetic circuitry that can detect uric acid in the bloodstream and process this information to produce a therapeutic response," the Independent quoted Fussenegger as saying.
Tests on laboratory mice have proved the efficacy of the new technique...
An apple a day...
Researchers from the University of Illinois fed laboratory mice low-fat diets that were identical, except that they contained either soluble or insoluble fibre. They found that soluble fibre reduces inflammation associated with obesity-related diseases and strengthens the immune system.
“Soluble fibre changes the personality of immune cells – they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection,” said Gregory Freund, professor at the college of medicine...
“Soluble fibre changes the personality of immune cells – they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection,” said Gregory Freund, professor at the college of medicine...
Overcoming Obesity
For dieters, it's sometimes impossible to resist your favorite foods. Like chocolate. And now some researchers working with mice think they have a clue as to why the temptation can get so strong.
After starving mice of food, scientists presented them with a highly desirable treat of chocolate — in an experiment designed to keep them from getting it. Each time the animals went for the sweet, they received a small foot shock. One group of starving mice learned to stop reaching for the chocolate after a few shocks, but another group went for the candy relentlessly, despite the negative consequences.
The difference between the two groups seemed to be levels of norepinephrine, a hormone and neurotransmitter released in the prefrontal cortex of the brain, which is involved in reward and satiety circuits. Norepinephrine plays an important role in compulsive behaviors associated with drug abuse, and also contributes to food-seeking behavior. In the chocolate trial, the treat-seeking mice had higher levels of norepinephrine than the mice who abandoned the chocolate. And when scientists used an inhibitor to inactivate the chemical in the chocolate-obsessed animals, their compulsive behavior stopped.
Doctors hope that by understanding the way biological processes reinforce maladaptive behaviors like obsessive eating, they can focus on new targets for treating obesity — targets that directly address the root causes of why some people continue to eat, even when they know they shouldn't.
After starving mice of food, scientists presented them with a highly desirable treat of chocolate — in an experiment designed to keep them from getting it. Each time the animals went for the sweet, they received a small foot shock. One group of starving mice learned to stop reaching for the chocolate after a few shocks, but another group went for the candy relentlessly, despite the negative consequences.
The difference between the two groups seemed to be levels of norepinephrine, a hormone and neurotransmitter released in the prefrontal cortex of the brain, which is involved in reward and satiety circuits. Norepinephrine plays an important role in compulsive behaviors associated with drug abuse, and also contributes to food-seeking behavior. In the chocolate trial, the treat-seeking mice had higher levels of norepinephrine than the mice who abandoned the chocolate. And when scientists used an inhibitor to inactivate the chemical in the chocolate-obsessed animals, their compulsive behavior stopped.
Doctors hope that by understanding the way biological processes reinforce maladaptive behaviors like obsessive eating, they can focus on new targets for treating obesity — targets that directly address the root causes of why some people continue to eat, even when they know they shouldn't.
Novel Method Eyed for Normalizing Blood Sugar
A potential new method of normalizing blood sugar levels in diabetes has been discovered by U.S. researchers.
The Children's Hospital Boston team identified a cellular pathway that fails because of obesity. Artificial activation of this pathway normalized glucose levels in severely obese and diabetic mice, according to the report published online March 28 in Nature Medicine.
Previously, the researchers found that the brain, liver and fat cells of obese mice have increased stress in the endoplasmic reticulum (ER), which produces proteins. Obesity overwhelms the ER and causes it to malfunction. This so-called "ER stress" triggers a series of events that suppresses the body's response to insulin, making ER stress an important link between obesity and type 2 diabetes...
The Children's Hospital Boston team identified a cellular pathway that fails because of obesity. Artificial activation of this pathway normalized glucose levels in severely obese and diabetic mice, according to the report published online March 28 in Nature Medicine.
Previously, the researchers found that the brain, liver and fat cells of obese mice have increased stress in the endoplasmic reticulum (ER), which produces proteins. Obesity overwhelms the ER and causes it to malfunction. This so-called "ER stress" triggers a series of events that suppresses the body's response to insulin, making ER stress an important link between obesity and type 2 diabetes...
Addicted to Fat: Overeating May Alter the Brain as Much as Hard Drugs
Like many people, rats are happy to gorge themselves on tasty, high-fat treats. Bacon, sausage, chocolate and even cheesecake quickly became favorites of laboratory rats that recently were given access to these human indulgences—so much so that the animals came to depend on high quantities to feel good, like drug users who need to up their intake to get high.
A new study, published online March 28 in Nature Neuroscience, describes these rats' indulgent tribulations, adding to research literature on the how excess food intake can trigger changes in the brain, alterations that seem to create a neurochemical dependency in the eater—or user. (Scientific American is part of Nature Publishing Group.) Preliminary findings from the work were presented at the Society for Neuroscience meeting in October 2009...
A new study, published online March 28 in Nature Neuroscience, describes these rats' indulgent tribulations, adding to research literature on the how excess food intake can trigger changes in the brain, alterations that seem to create a neurochemical dependency in the eater—or user. (Scientific American is part of Nature Publishing Group.) Preliminary findings from the work were presented at the Society for Neuroscience meeting in October 2009...
Fried breakfast is healthiest start to day, say scientists
Scientists believe that breakfast programmes the metabolism for the rest of the day, and a fatty meal will help the body break down fat later on.
Carbohydrate rich foods in contrast appear mainly to prepare the body to break down only carbohydrates, the International Journal of Obesity reports.
Dr Martin Young, of the University of Alabama at Birmingham, said: “The first meal you have appears to programme your metabolism for the rest of the day.
“This study suggests that if you ate a carbohydrate-rich breakfast it would promote carbohydrate utilisation throughout the rest of the day, whereas if you have a fat-rich breakfast, you (can) transfer your energy utilisation between carbohydrate and fat.”
The team of researchers found there may be some truth in the old saying “'eat breakfast like a king, lunch like a prince and dinner like a pauper' – may be the key to a healthy body and mind.”
Their study looked at the effects of eating different types of food – and of eating them at different times in the day, according to the Daily Mail.
Mice fed a high fat meal after waking remained healthy, but those given a carb-rich breakfast, followed by a fatty dinner, did not fare as well...
Carbohydrate rich foods in contrast appear mainly to prepare the body to break down only carbohydrates, the International Journal of Obesity reports.
Dr Martin Young, of the University of Alabama at Birmingham, said: “The first meal you have appears to programme your metabolism for the rest of the day.
“This study suggests that if you ate a carbohydrate-rich breakfast it would promote carbohydrate utilisation throughout the rest of the day, whereas if you have a fat-rich breakfast, you (can) transfer your energy utilisation between carbohydrate and fat.”
The team of researchers found there may be some truth in the old saying “'eat breakfast like a king, lunch like a prince and dinner like a pauper' – may be the key to a healthy body and mind.”
Their study looked at the effects of eating different types of food – and of eating them at different times in the day, according to the Daily Mail.
Mice fed a high fat meal after waking remained healthy, but those given a carb-rich breakfast, followed by a fatty dinner, did not fare as well...
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