A high-fat diet may not always pack on the pounds, new research from the Warren Alpert Medical School suggests. By successfully preventing weight gain in mice, researchers have shed light on obesity prevention in humans. The study was released online last week and will be published in the January 2012 issue of Endocrinology, a science journal.
Even though the mice were on a high-fat diet, researchers were able to significantly reduce their weight gain by activating a human enzyme called IKKbeta in their fatty tissue. The enzyme normally triggers immune responses, such as inflammation, following increases in the number of human fat cells.
Researchers were curious to see what would happen if they reversed the order of events by activating the enzyme prior to weight gain.
They found that in addition to reduced weight gain, the mice with the activated enzyme also had faster metabolisms. In these mice, insulin was more effective at lowering blood sugar than it was in the mice that had not been treated.
The activated enzyme also inhibited resistance to insulin, another side effect of obesity.
The study has definite implications for helping people who suffer from conditions characterized by insulin resistance, such as Type 2 diabetes patients, said Haiyan Xu, assistant professor of medicine...
Saturday, December 17, 2011
New Weight-Loss Drug Reduces Body Weight in Monkeys, Mice
Researchers at the University of Texas MD Anderson Cancer Center have developed a drug that assaults the blood supply of fat cells and led to weight loss in obese rhesus monkeys.
Renata Pasqualini, Ph.D., co-senior author of the study and professor in MD Anderson's David H. Koch Center for Applied Research for Genitourinary Cancers, along with Wadih Arap, M.D., co-senior author of the study and a professor in the Koch Center, and Kirstin Barnhart, D.V.M., Ph.D., veterinary clinical pathologist at MD Anderson's Keeling Center for Comparative Medicine and Research, have created a new weight-loss drug that could potentially reduce accumulated white fat in humans.
Currently, weight-loss drugs work to suppress the appetite or increase metabolism in order to combat obesity, but harmful side effects come with the use of such drugs.
Now, Pasqualini and Arap have designed a new drug called Adipotide, which attacks white adipose tissue. This tissue is an unhealthy kind of fat that accumulates around the abdomen and under the skin. Adipotide contains a homing agent that attaches to a protein on the surface of blood vessels that support the fat. A synthetic peptide then triggers cell death, and with a lack of blood supply, the fat cells are reabsorbed.
The drug was used in mice models and rhesus monkey models. Adipotide was able to decrease abdominal circumference, body mass index (BMI) and body fat.
According to the study, the obese mice lost about 30 percent of their body weight while on Adipotide. The rhesus monkeys in the study, which were "spontaneously" obese due to overeating and a lack of physical activity, had a 27 percent decrease in abdominal fat levels. The drug reduced the weight of rhesus monkeys by 11 percent in just one month...
Renata Pasqualini, Ph.D., co-senior author of the study and professor in MD Anderson's David H. Koch Center for Applied Research for Genitourinary Cancers, along with Wadih Arap, M.D., co-senior author of the study and a professor in the Koch Center, and Kirstin Barnhart, D.V.M., Ph.D., veterinary clinical pathologist at MD Anderson's Keeling Center for Comparative Medicine and Research, have created a new weight-loss drug that could potentially reduce accumulated white fat in humans.
Currently, weight-loss drugs work to suppress the appetite or increase metabolism in order to combat obesity, but harmful side effects come with the use of such drugs.
Now, Pasqualini and Arap have designed a new drug called Adipotide, which attacks white adipose tissue. This tissue is an unhealthy kind of fat that accumulates around the abdomen and under the skin. Adipotide contains a homing agent that attaches to a protein on the surface of blood vessels that support the fat. A synthetic peptide then triggers cell death, and with a lack of blood supply, the fat cells are reabsorbed.
The drug was used in mice models and rhesus monkey models. Adipotide was able to decrease abdominal circumference, body mass index (BMI) and body fat.
According to the study, the obese mice lost about 30 percent of their body weight while on Adipotide. The rhesus monkeys in the study, which were "spontaneously" obese due to overeating and a lack of physical activity, had a 27 percent decrease in abdominal fat levels. The drug reduced the weight of rhesus monkeys by 11 percent in just one month...
Scripps Research scientists uncover new role for gene in maintaining steady weight
Against the backdrop of the growing epidemic of obesity in the United States, scientists from the Florida campus of The Scripps Research Institute have made an important new discovery regarding a specific gene that plays an important role in keeping a steady balance between our food intake and energy expenditure. The study may help scientists better understand the keys to fighting obesity and related disorders such as diabetes. The study, which was published in the November 25, 2011 print edition of The Journal of Biological Chemistry, focused on the melanocortin-3 receptor (MC3R), which normally responds to signals of nutrient intake.
"What we discovered was quite a surprise," said Scripps Research Associate Professor Andrew Butler, who led the study. "We thought that the actions of the receptor expressed in the brain would be critical for metabolic homeostasis. However, what we found is that actions of the receptor expressed outside the brain appear to be equally important."
The existence of drug targets in areas outside of the central nervous system (the body's "periphery") might help in the effort to develop drugs that influence metabolism without major side effects, Butler said.
The findings were made possible by the team's development of a new transgenic animal model, where expression of the MC3R gene can be selectively "switched on" in different cell types.
In the study, the suppression of MC3R expression in the brain and peripheral tissues had a marked impact on metabolic homeostasis (equilibrium). Interestingly, mice expressing the MC3R gene in the brain only displayed an obese phenotype (physical appearance) similar to those where all types of expression was suppressed, indicating that actions of this receptor in the brain are not sufficient to protect against weight gain.
"What we discovered was quite a surprise," said Scripps Research Associate Professor Andrew Butler, who led the study. "We thought that the actions of the receptor expressed in the brain would be critical for metabolic homeostasis. However, what we found is that actions of the receptor expressed outside the brain appear to be equally important."
The existence of drug targets in areas outside of the central nervous system (the body's "periphery") might help in the effort to develop drugs that influence metabolism without major side effects, Butler said.
The findings were made possible by the team's development of a new transgenic animal model, where expression of the MC3R gene can be selectively "switched on" in different cell types.
In the study, the suppression of MC3R expression in the brain and peripheral tissues had a marked impact on metabolic homeostasis (equilibrium). Interestingly, mice expressing the MC3R gene in the brain only displayed an obese phenotype (physical appearance) similar to those where all types of expression was suppressed, indicating that actions of this receptor in the brain are not sufficient to protect against weight gain.
Neuron Transplant Reduces Obesity In Mice
Scientists at Harvard University have successfully transplanted neurons into the brains of obesity-prone mice to prevent them from getting fat. The researchers did not have human obesity in mind when conducting the experiment; rather, they used the neuron transplant as an example of a method to restore function to abnormal neural circuits. The results have highlighted the promise in cell therapies. For example, scientists could soon transplant stem cells or fetal cells to treat nervous system diseases.
Throughout the years, research on cell therapies has rarely found success. Experiments using stem cell therapy to treat spinal injuries as well as some trials involving fetal cell therapy for Parkinson’s disease have yielded no positive results. Only until recent years has it been proven that the human brain produces new neurons throughout the lifetime. Some evidence has shown that these new neurons are occasionally integrated into existing neural circuits and actually enhance brain function. This evidence led scientists to postulate that this could be done using transplanted cells as well.
Obesity prone mice were used to test a special fetal stem cell therapy. | Photo courtesy of Bigplankton via Wikimedia Commons
The Harvard University scientists extracted healthy neurons from mouse embryos (the hypothalamus to be exact) and transplanted those neurons into the same region of the brain in obesity prone mice. These mice lack the receptor for leptin, a hormone that regulates metabolism and body weight, and therefore they are prone to being diabetic and obese. The transplanted neurons were labeled with a green fluorescent protein to track them in the neural circuit. The results were quite promising, as the transplanted neurons were able to integrate efficiently into the existing neural circuit and develop into mature neurons that responded to leptin. At the end of the experiment, the treated mice weighed 30% less than mice that had not received a transplant. This suggested that the transplanted neurons actually fixed the damaged neural circuit.
Though the experiment was not directed towards treating human obesity, the success of the experiment gave scientists a light at the end of the tunnel in terms of cell therapies...
Throughout the years, research on cell therapies has rarely found success. Experiments using stem cell therapy to treat spinal injuries as well as some trials involving fetal cell therapy for Parkinson’s disease have yielded no positive results. Only until recent years has it been proven that the human brain produces new neurons throughout the lifetime. Some evidence has shown that these new neurons are occasionally integrated into existing neural circuits and actually enhance brain function. This evidence led scientists to postulate that this could be done using transplanted cells as well.
Obesity prone mice were used to test a special fetal stem cell therapy. | Photo courtesy of Bigplankton via Wikimedia Commons
The Harvard University scientists extracted healthy neurons from mouse embryos (the hypothalamus to be exact) and transplanted those neurons into the same region of the brain in obesity prone mice. These mice lack the receptor for leptin, a hormone that regulates metabolism and body weight, and therefore they are prone to being diabetic and obese. The transplanted neurons were labeled with a green fluorescent protein to track them in the neural circuit. The results were quite promising, as the transplanted neurons were able to integrate efficiently into the existing neural circuit and develop into mature neurons that responded to leptin. At the end of the experiment, the treated mice weighed 30% less than mice that had not received a transplant. This suggested that the transplanted neurons actually fixed the damaged neural circuit.
Though the experiment was not directed towards treating human obesity, the success of the experiment gave scientists a light at the end of the tunnel in terms of cell therapies...
Weight-Loss Enzyme Identified by Brown Researchers
While not the solution to holiday weight gain, a new study from Brown University researchers sheds promising new light on metabolism and weight loss.
Scientists report that they substantially curbed weight gain, improved metabolism, and improved the efficacy of insulin in mice by engineering them to express a specific human enzyme in their fat tissue. Although the obesity prevention came at the significant cost of widespread inflammation, the research offers new clues about the connections among obesity, insulin resistance and type 2 diabetes, and inflammation...
Scientists report that they substantially curbed weight gain, improved metabolism, and improved the efficacy of insulin in mice by engineering them to express a specific human enzyme in their fat tissue. Although the obesity prevention came at the significant cost of widespread inflammation, the research offers new clues about the connections among obesity, insulin resistance and type 2 diabetes, and inflammation...
Cilia control eating signal
The action of tiny hairlike appendages on cells can mean the difference between fat and thin. Now scientists have a better idea of how the little hairs, called primary cilia, control appetite.
Primary cilia — single, hairlike projections that all cells in vertebrates usually have — seem to sequester a protein that senses and responds to an appetite-stimulating hormone, Nicolas Berbari of the University of Alabama at Birmingham reported December 6 at the annual meeting of the American Society for Cell Biology. In people and mice that lack primary cilia, the appetite stimulant works overtime, leading to overeating and obesity, Berbari said.
These findings may lead to new ways to control appetite and prevent or reverse obesity.
And the study may help scientists better understand the process of eating, said Kirk Mykytyn, a cell biologist at Ohio State University in Columbus. “This work is important because it’s more thoroughly clarifying the molecular mechanism involved in obesity associated with the loss of cilia,” he said...
Primary cilia — single, hairlike projections that all cells in vertebrates usually have — seem to sequester a protein that senses and responds to an appetite-stimulating hormone, Nicolas Berbari of the University of Alabama at Birmingham reported December 6 at the annual meeting of the American Society for Cell Biology. In people and mice that lack primary cilia, the appetite stimulant works overtime, leading to overeating and obesity, Berbari said.
These findings may lead to new ways to control appetite and prevent or reverse obesity.
And the study may help scientists better understand the process of eating, said Kirk Mykytyn, a cell biologist at Ohio State University in Columbus. “This work is important because it’s more thoroughly clarifying the molecular mechanism involved in obesity associated with the loss of cilia,” he said...
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