Why men and women gain weight in different areas of the body

Why is it that men and women put on those extra kilos in different areas of the body? The answer may not be far away as researchers are close to revealing vital sex differences in men and women concerning fat storage.

The research has indicated that fat is genetically different in men and women.

"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," said Deborah Clegg, of the UT Southwestern Medical Center.

"The notion that fat cells between males and females are alike is inconsistent with our findings," he said.

Mice store their fat similar to humans in a sexually dimorphic pattern. Just like human males, male mice store their fat in the belly and midsection area while females store fat in their hips, thighs and buttocks...

Exercise 'can control appetite'

Exercise not only burns off calories, it can reduce feelings of hunger, scientists have said.

The findings suggest a "double whammy" benefit that may help the overweight to slim.

Researchers studying obese mice found that exercise restored the sensitivity of brain cells involved in controlling appetite.

The change increased satiety - or "feeling full" - in the animals and led to a reduction in food intake...

Novel Diabetes Hope Comes from Chinese Herbs

Emodin, a natural product that can be extracted from various Chinese herbs including Rheum palmatum and Polygonum cuspidatum, shows promise as an agent that could reduce the impact of type 2 diabetes. Findings published in this month's edition of the British Journal of Pharmacology show that giving emodin to mice with diet-induced obesity lowered blood glucose and serum insulin, improved insulin resistance and lead to more healthy levels of lipid in the blood. It also decreased body weight and reduced central fat mass..

Wouldn’t it be Great if You Could Pop a Pill and Lose Weight?

And wouldn't it be great if that pill weren't something advertised on late-night TV, but rather a legitimate treatment? A drug called rimonabant, introduced in Europe, seemed to fit the bill at first, but it was pulled from the market in late 2008 due to concerns about psychiatric side effects.

The story doesn't end there, though. New research on animals suggests that a second generation of drugs may treat obesity without those side effects. A presentation at the International Congress on Obesity in Stockholm, Sweden, revealed a treatment that has the same weight-loss effect as rimonabant, but without impacting the brain.

What's different? The new drug, currently called TM38837, does not affect peripheral organs and tissues. Rimonabant, however, didn't discriminate. According to earlier research, rimonabant doubled the risk of disorders such as depression and suicide.

In their new work, scientists tried the second-generation drug on mice and rats. After a five-week course of treatment, the mice had lost 22 to 26 percent more weight than mice in a control group. The rats had lost 14 percent more than the controls. In both cases, weight loss from TM38837 was the same as weight loss from rimonabant. Separate studies, including dissections and behavioral tests, showed that the drug was less likely to impact the brains of test animals...

Light Shed on Triglyceride Metabolism

New findings reported in the July issue of Cell Metabolism, are offering new leads as to why some people might suffer from high levels of triglycerides. High triglycerides are a risk factor for atherosclerosis and cardiovascular disease. They can also lead to inflammation of the pancreas, the researchers said...

It seems that a protein known as GPIHBP1 is the key. Mice lacking that protein end up with LPL built up outside of their muscle and fat tissue instead of where it belongs in capillaries. They show that GPIHBP1 normally sits on the surface of capillary cells, where it actively transports LPL.

The new findings offer an explanation for what had been a surprising finding; Gpihbp1-deficient mice develop severe hypertriglyceridemia, even when they eat a normal diet of mouse chow. Very recently, other researchers have also shown that some people with elevated triglyceride levels carry mutations in their GPIHBP1 gene...

Calling all Obelixes! Hope at home - Indian researchers join global scramble to develop anti-obesity pill

New Delhi, July 31: A team of industry researchers in India has synthesised novel compounds that interfere with weight-gaining mechanisms in the body and joined an international scramble to develop a new class of anti-obesity pills.

The team at Dr Reddy’s Laboratories (DRL), Hyderabad, has shown in laboratory studies that one of these compounds, code-named 22g, helped gluttonous and obese mice lose 8 per cent of their body weight after seven days of oral medication...

ew loci for blood lipids identified; functional role of 1p13 locus detailed

Bethesda, MD and Boston, MA - Two new studies published this week provide further insights into the genetic underpinnings of variations in blood lipid levels [1,2]. In one large-scale genomewide association study (GWAS), researchers identified 95 loci that showed associations with blood lipid levels, while another group performed a detailed functional genomics analysis showing how a locus on chromosome 1p13, previously associated with low LDL-cholesterol levels and MI, regulates LDL-cholesterol levels.

"The two papers are highly complementary," Dr Sekar Kathiresan (Massachusetts General Hospital, Boston), a senior investigator of both studies, told heartwire. "The reason they're so complementary is that the first paper, the GWAS paper, puts down 95 stakes in the sand, while the second paper drills down on one of those stakes. We think the mapping effort, the GWAS paper, is incredibly important simply based on the scale of the effort. It's safe to say it's the largest genetics study done to date, and these 95 loci explain about 25% of the genetic component for lipid levels, which is among the largest proportion of variation evaluated to date."

The two studies are published in the August 5, 2010 issue of Nature...

To show that SORT1 is the causal gene, the researchers manipulated the gene in mice. With small interfering RNA "knockdown" and "viral overexpression" in the mouse liver, the researchers showed that the upregulation of SORT1 led to significantly lower LDL-cholesterol levels, as much as 80% lower, and that silencing SORT1 increased LDL cholesterol approximately 200%.

"Using these experiments in mice, we were able to prove that sortilin is the right gene for the LDL effect at the chromosome 1 locus," Kathiresan told heartwire. "And then, finally, if sortilin is the right gene, how does sortilin lower LDL cholesterol? We showed that the physiologic mechanism is that higher levels of sortilin lead to less secretion of very low-density lipoprotein (vLDL) from the liver, and vLDL is the precursor to LDL. Having less of the precursor around leads to less LDL, and this was the final piece of the puzzle."...

All-Nighters May Increase Fat Levels in Blood

Disruptions to a person's normal sleep cycle, such as pulling several all-nighters, could lead to an increase in harmful triglycerides in the blood, a new study on mice suggests.

Though further studies are needed to firm up whether the same holds for humans, scientists often use these rodents as models for human systems.

The new findings could have implications for understanding the health effects of night shifts, 14-hour work days and transoceanic flights. High levels of triglycerides in the blood are a risk factor for heart disease and obesity – not only in mice, but also potentially in people, the researchers say...

Insufficient ALA could be linked to obesity trend

A new study suggests that a deficiency in alpha-linoleic acid (omega-3) coupled with a chronic excess of linoleic acid (omega-6) could lead to ‘inherited obesity’.
The study, published in the Journal of Lipid Research, describes an increase in fat mass of mice over several generations when fed an ‘unbalanced Western diet’.

In addition to trans-generational weight gain, the research also observed the onset of metabolic disorders such as insulin resistance, and the expression of the inflammatory genes involved in obesity as generations advanced.

“Collectively, our data show that continuous exposure to a high-fat diet combined with a high LA:LNA [omega-6:omega-3] ratio over generations triggers a discrete and steady increase in inflammatory stimuli, accompanied by enhancement of fat mass” wrote the researchers.

Unbalanced Intake

The beneficial role that polyunsaturated fatty acids can have on health is well established. However when their intake is unbalanced, these essential fatty acids can enhance factors that can induce obesity, and may have serious long-term effects on human health.

During the last forty years Western societies have seen increases in the level of calories ingested, alongside an increase of over 250 percent in levels omega-6 intake and a fall in levels of omega-3 of 40 percent. This change in diet has coincided with a steady rise in obesity levels through the generations.

Over this time the ratio of omega-6 to omega-3 in a typical Western diet has shifted from the recommended 5-to-1, to 15-to-1 in much of Europe, and can be as high as 40-to-1 in the United States.

Alpha-linoleic acid (ALA) omega-3 is an essential fatty acid that the body cannot make, and therefore must be consumed in the diet. Good sources of ALA include: flaxseed, soybeans, walnuts, and olive oil. The U.S Institute of Medicine recommends an ALA intake of 1.6 grams per day for men and 1.1 grams per day for women.

Assessing the consequences

The new research, led by Gérard Ailhaud at the Université de Nice Sophia-Antipolis in France, exposed several generations of mice to a high omega-6 and low omega-3 "Western" diet and assessed the consequences.

The mice were given unrestricted access to food and water (ad libitum conditions) over several generations in order to allow the mice to self-regulate the intake according to biological needs.

“We chose purposely ad libitum conditions to expose both male and female mice across several generations to a Western-like diet” the researchers explain.

Trans-generational inheritance

The results of the study observe that under conditions of genetic stability and with no change to routine, four generations of a ‘Western-like fat diet’ were sufficient to gradually increase fat mass.

“A gradual trans-generational increase in adiposity can occur in mice fed a Western-like fat diet” wrote the researchers.

The study suggests that an unbalanced diet can lead to changes in the expression of genes that control growth and immune functions.

A gene expression analysis of fat tissue over several generations of the mice observed “discrete and steady changes in certain important players, such as colony stimulating factor-3 (CSF3) and Nocturnin.”

The researchers said “Our data show that expression of CSF-3 increased over generations in mice. These results strongly suggest a role for CSF-3 in stimulating growth of adipocyte progenitors.”...

Meals as Medicine: Anti-Obesity Effects of Soy in Rat Model of Menopause

Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior, finds that a diet rich in soy prevents weight gain in post-menopausal female rats.

Previous research suggests that reduced levels of the hormone estrogen during menopause are responsible for the increased body weight and abdominal fat often experienced by postmenopausal women. However, while estrogen replacement therapies can reduce weight gain, they also have unwelcome side effects, prompting a search for alternative methods of treatment. Soy naturally contains estrogen-like compounds called phytoestrogens, and so dietary soy may provide an alternative to typical estrogen replacement therapies...

New obesity compound shows promise in mice

A compound similar to the once-promising weight loss drug Acomplia helped obese mice lose weight and lower their blood fats and blood sugar without causing psychological side effects, U.S. researchers said on Monday.

Like Acomplia, the drug targets cannabinoid receptors that become active after smoking marijuana, but the team tinkered with the compound to keep it from crossing over into the brain, reducing the risk of depression, anxiety or other neurological problems seen in the original drug.

While obese mice do not lose as much weight on this new compound, it was just as effective as Acomplia in reducing obesity-related metabolic changes, researchers from the National Institutes of Health and Northeastern University reported in the Journal of Clinical Investigation...

Resveratrol revs up metabolism, promotes weight loss in first ever primate study

Resveratrol is a type of phytonutrient known as a polyphenol. Found in the skin of grapes, wine, grape juice, peanuts, and berries, it has often been hailed as a life-extending natural compound. After all, research in mice and lab rats has indicated it can protect those animals from obesity and diabetes and has anti-cancer, anti-inflammatory and blood-sugar-lowering effects, too. However, rats and mice are rodents -- and their physiology is in many ways different from the primate family that includes apes, monkeys and, most importantly, human beings...

Scientists find unsuspected molecular link between obesity and insulin resistance

A new understanding of insulin resistance and the action of diabetes drugs such as Avandia and Actos could pave the way for improved medications that are more selective and safer, say scientists from Dana-Farber Cancer Institute and The Scripps Research Institute.

Our findings strongly suggest that good and bad effects of these drugs can be separated by designing second-generation drugs that focus on the newly uncovered mechanism, said Bruce Spiegelman, PhD, of Dana-Farber, senior author on a report appearing in the July 22 issue of Nature.

Avandia and Actos, known generically as rosiglitazone and pioglitazone, are widely used to counteract the obesity-related abnormalities in insulin response that lead to diabetes. The drugs act on a master regulatory protein called PPAR-gamma, primarily in fat cells, which governs genes involved in the bodys response to insulin.

Obesity resulting from a high-fat diet alters the function of PPAR-gamma and disrupts the expression of those insulin response genes, including adipsin and adiponectin. Avandia and Actos work by binding to PPAR-gamma and reversing the gene expression changes.

The drugs were believed to work by stimulating or agonizing the PPAR-gamma receptor, causing it to rev up some genes and dampen the activity of others.

In the Nature report, however, the researchers say they have identified an entirely new and surprising mechanism by which PPAR-gamma can control whole-body insulin sensitivity. It is mainly through this mechanism, they found, that the diabetes drugs counteract insulin resistance – not their agonist effect on PPAR-gamma. Moreover, they say, agonism of PPAR-gamma may be largely responsible for the harmful drug side effects.

The newly identified pathway linking obesity and insulin response involves cdk5, a protein kinase, or molecular switch. When cdk5 is activated by the development of obesity in mice, it causes a chemical change in PPAR-gamma called phosphorylation. In contrast to agonism of PPAR-gamma, phosphorylation has a narrow effect, disrupting a smaller set of genes that lead to insulin resistance...

Lose sleep, get fat?

LOS ANGELES — Disrupted sleep patterns seem to contribute to the risk of obesity and diabetes, according to numerous studies. Researchers have theorized that disrupted circadian rhythms throw off various hormonal processes in the body that contribute to disease.

This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at University of Texas Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.

One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels.

The study shows that disruption of these genes only in the pancreas causes early signs of diabetes...

AMRI Announces Phase I Study of Novel Drug for Obesity Treatment

ALBANY, N.Y., Jul 21, 2010 (BUSINESS WIRE) -- AMRI (AMRI 6.86, +0.34, +5.21%) has commenced enrollment for a Phase I study of ALB-127158(a), a novel MCH1 receptor antagonist offering a potential new approach for the treatment of obesity. The announcement was made yesterday during a presentation by AMRI's Dr. Peter Guzzo, director, discovery research and development, at the 6th Obesity and Diabetes Drug Development Summit in Arlington, VA. Preclinical data were also reported.

The clinical trial will be comprised of a single ascending dose study followed by a multiple ascending dose study to assess safety, tolerability and pharmacokinetics. The multiple ascending dose study will be conducted in overweight subjects to evaluate pharmacodynamics (the physiological effects of the drug candidate on the body), including caloric intake, hunger assessments and metabolic markers. The Phase I study is anticipated to be completed during the first quarter of 2011.

Preclinical studies of the AMRI compound have suggested promise for the treatment of human obesity. For example, in data presented by Dr. Guzzo, ALB-127158(a) showed high levels of MCH1 receptor occupancy leading to a sustained, dose-related reduction in food intake in dietary-induced obese mice. The ensuing weight loss of up to 18% after 28 days of administration was substantially higher than that from the currently available therapeutic agent, sibutramine. Weight loss was shown to be entirely due to a reduction in food intake leading to a preferential reduction in fat stores and was accompanied by significant improvements in glucose tolerance. Preliminary safety evaluation, including cardiovascular safety, was also reported; subsequent regulatory safety testing supported approval by the UK Medicines and Healthcare Products Regulatory Agency for initiation of the Phase I study...

Good news for Obese people

WASHINGTON: Researchers at Washington University School of Medicine in St Louis have found a way to significantly reduce atherosclerosis in mice without lowering cholesterol levels or eliminating other obesity-related problems.

Atherosclerosis is the process through which fatty substances, such as cholesterol and cellular waste products accumulate in the lining of arteries.

Those buildups, called plaques, reduce blood flow through the artery and can contribute to heart attack, stroke and even gangrene. It is common in individuals with obesity-related problems such as high blood pressure, high cholesterol and diabetes.

In the study, researchers inhibited atherosclerosis in mice by interfering with production of a substance called fatty acid synthase.

This enzyme converts dietary sugars into fatty acids in the liver, where it plays an important role in energy metabolism.

But fatty acids also are involved in atherosclerosis.

"The plaques that clog arteries contain large amounts of fatty acids. We engineered mice that are unable to make fatty acid synthase in one of the major cell types that contribute to plaque formation. On a standard Western diet high in fat, the mice had less atherosclerosis than their normal littermates," said senior investigator Dr. Clay F. Semenkovich.

Animals can't survive without fatty acid synthase, so mice in this study were able to make the substance in most of their tissues.

They couldn't manufacture it, however, in macrophages, a type of white blood cell that surrounds and kills invading microorganisms, removes dead cells from the body and stimulates the action of other immune cells.

These mouse experiments suggest targeting fatty acid synthase in macrophages may provide a potential treatment strategy for humans.

The researchers identified factors in the fatty acid pathway that seem to be capable of preventing plaques from blocking arteries in mice.

He says those substances - LXR-alpha and ABCA1 - eventually may become drug targets.

"It may be possible, for example, to take macrophages out of humans, inhibit fatty acid synthase in those cells, and then infuse the macrophages back into the same personFrom what we've observed in mice, we would hypothesize that approach might prevent or interfere with plaque buildup in people," he said...

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...

Study Suggests Brown Adipose Tissue Involved in Increased Energy Expenditure after Capsinoids Ingestion

Ajinomoto Co., Inc. and a group led by professor Masayuki Saito of Tenshi College in Sapporo, Japan have found that a single ingestion of capsinoids, a sweet chili pepper extract, appears to increase energy expenditure, especially in people with a high level of activity in brown adipose tissue. The research results were presented at the XI International Congress on Obesity 2010 (ICO 2010) on July 13 in Stockholm, Sweden.

The finding may have implications for controlling obesity, which is affected by the activation of brown adipose tissue according to recent studies.

Previous research with animals such as mice has shown that brown adipose tissue is involved in the regulation of energy expenditure and changes in body-fat levels. Brown adipose tissue in humans and several types of animals is mainly located around the neck and large blood vessels of the thorax. Fat is broken down in the mitochondria of brown adipose tissue cells to generate body heat. Although brown adipose tissue exists to some degree in human infants, the once-conventional view was that the tissue gradually deteriorates and is barely detectable in adults, with virtually no physiological role. In recent years, however, the group led by professor Saito has used PET imaging1 to confirm that brown adipose tissue is present in adults...

Omega imbalance can make obesity 'inheritable': study

Overeating combined with the wrong mix of fats in one's diet can cause obesity to be carried over from one generation to the next, researchers in France reported Friday.

Omega-6 and omega-3, both polyunsaturated fatty acids, are each critical to good health.
But too much of the first and not enough of the second can lead to overweight offspring, the scientists showed in experiments with mice designed to mirror recent shifts in human diet.

Over the last four decades, the ratio of omega-6 to omega-3 in a typical Western diet has shifted from a healthy five-to-one to 15-to-one in much of Europe, and up to 40-to-one in the United States.

In the breast milk of American women, the average ratio has gone from six-to-one to 18-to-one.
Earlier studies have established a link between such imbalances and heart disease.

But "this is the first time that we have shown a trans-generational increase in obesity" linked to omega intake, said Gerard Ailhaud, a biochemist at the University of Nice-Sophia Antipolis and main architect of the study.
"Omega six is like a fat-producing bomb," he told AFP by phone.
Experts differ on whether obesity is more importantly due to the percentage of fat in one's diet or the sheer amount of calories consumed.
The findings, published in the US-based Journal of Lipid Research, add yet another dimension to the debate, and could shed new light on the obesity epidemic that has swept across the globe, mainly in rich nations.

They also suggest that persistence within families of health-threatening weight gain -- while not genetic in origin -- may not be entirely due to environmental factors either.

The link between omega imbalance and obesity "is probably epigenetic," said Ailhaud, referring to the complex process whereby the information in genes is translated into chemical activity.

"The genome and the DNA of the rodents has not been modified, but these factors can influence the way in which certain genes are expressed."

In the experiments, four generations of mice were fed a 35-percent fat diet with the omega imbalance now found in much of the developed world.

The result was progressively fatter mice at birth, generation after generation...

Disrupted sleep patterns could add to risk of obesity, diabetes

Disrupted sleep patterns seem to contribute to the risk of obesity and diabetes, according to numerous studies. Researchers have theorized that disrupted circadian rhythms throw off various hormonal processes in the body that contribute to disease.

This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at UT Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.

One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels...