 |
|
Research provides clues to obesity's cause and hints of new approach for curbing appetite
April 10, 2006Pittsburgh - Hot fudge sundaes and french fries aside, new research suggests obesity is due at least in part to an attraction between leptin, the hormone that signals the brain when to stop eating, and a protein more recently associated with heart disease. Reporting in Nature Medicine, University of Pittsburgh researchers provide evidence that C-reactive protein (CRP) not only binds to leptin but its hold impairs leptin's role in controlling appetite. The results may help explain why obese people have so much trouble losing weight as well as point to a different target for the pharmaceutical treatment of obesity.
"There's been a lot of interest in leptin as a means to curb appetite and reduce weight but clinical trials have had disappointing results. Our studies suggest an approach that should be further studied is one that disrupts the interaction between leptin and CRP, thereby restoring leptin's ability for signaling. We need to better understand how this interaction works and investigate the underlying mechanisms involved," said Allan Z. Zhao, Ph.D., assistant professor of cell biology and physiology, University of Pittsburgh School of Medicine, and the study's senior author.
Leptin is secreted by fat - the more fat, the more leptin - yet it is named for the Greek word leptos, which means "thin." In a region of the brain called the hypothalamus, leptin binds to receptors residing on the surface of neurons, setting off signals that tell the brain to stop eating and the body to expend energy by burning calories. While obese people produce much higher levels of leptin than thin and normal-weight individuals, they are somehow resistant to its effects. Dr. Zhao and his co-authors believe the binding of CRP to leptin may be the reason this is so. Their argument seems all the more plausible since CRP also is elevated in obese people. CRP, which is produced by the liver and typically rises as part of the immune system's inflammatory response, is gaining favor as a marker for hypertension and heart disease risk, known complications of obesity.
"We know that CRP binds to leptin, and this impairs its signaling, but we don't know how this is so. It may be that the coupling of the two makes crossing the blood-brain barrier difficult, or it may be that as a package it can't bind to leptin receptors in the brain," suggested Dr. Zhao.
Dr. Zhao and his collaborators sought to find factors normally circulating in blood that could inhibit leptin. CRP was the most potent of the five serum leptin-interacting proteins they identified.
In one set of studies, the researchers delivered human leptin continuously for six days into mice with receptors for leptin but without the ability to produce it. As expected, the plump mice ate less and lost weight, and their blood glucose levels normalized. Infusions containing both leptin and high doses of CRP blocked the action of leptin. The mice continued feasting, getting even fatter, and were no longer protected against diabetes. Giving CRP alone affected neither food intake nor body weight.
In a different experiment, the researchers found that when exposed to leptin, human liver cells increased their expression of CRP, suggesting that appetite may be regulated through a feedback loop that includes the liver in addition to the brain and fat cells that secrete leptin.
One of the many questions yet to be answered is whether too much fat increases CRP or if it's the high levels of CRP that make one fat. Dr. Zhao and his team are continuing their laboratory studies but they also plan to follow the outcomes of obese patients who are being treated with statin drugs, such as Lipitor and Zocor, for high cholesterol. Recent studies have found that statin drugs lower levels of CRP as well. Working with David E. Kelly, M.D., professor of medicine and director of the Obesity and Nutrition Research Center at the University of Pittsburgh and a co-author of the current paper, Dr. Zhao hopes to learn if such drugs might also help in reducing weight.
University of Pittsburgh Medical Center
"We know that CRP binds to leptin, and this impairs its signaling, but we don't know how this is so. It may be that the coupling of the two makes crossing the blood-brain barrier difficult, or it may be that as a package it can't bind to leptin receptors in the brain," suggested Dr. Zhao.
Dr. Zhao and his collaborators sought to find factors normally circulating in blood that could inhibit leptin. CRP was the most potent of the five serum leptin-interacting proteins they identified.
In one set of studies, the researchers delivered human leptin continuously for six days into mice with receptors for leptin but without the ability to produce it. As expected, the plump mice ate less and lost weight, and their blood glucose levels normalized. Infusions containing both leptin and high doses of CRP blocked the action of leptin. The mice continued feasting, getting even fatter, and were no longer protected against diabetes. Giving CRP alone affected neither food intake nor body weight.
In a different experiment, the researchers found that when exposed to leptin, human liver cells increased their expression of CRP, suggesting that appetite may be regulated through a feedback loop that includes the liver in addition to the brain and fat cells that secrete leptin.
One of the many questions yet to be answered is whether too much fat increases CRP or if it's the high levels of CRP that make one fat. Dr. Zhao and his team are continuing their laboratory studies but they also plan to follow the outcomes of obese patients who are being treated with statin drugs, such as Lipitor and Zocor, for high cholesterol. Recent studies have found that statin drugs lower levels of CRP as well. Working with David E. Kelly, M.D., professor of medicine and director of the Obesity and Nutrition Research Center at the University of Pittsburgh and a co-author of the current paper, Dr. Zhao hopes to learn if such drugs might also help in reducing weight.
University of Pittsburgh Medical Center
Obesity Current Events and Obesity News RSSBariatric surgery may resolve liver disease
Obesity is a growing epidemic in the U.S. with a significant increase in prevalence from 15 percent to 32.9 percent from 1980 to 2004. Nonalcoholic fatty liver disease (NAFLD) is an emerging problem related to the obesity epidemic, becoming one of the most common causes of liver disease in the nation.
Persistent pollutant may promote obesity
Tributyltin, a ubiquitous pollutant that has a potent effect on gene activity, could be promoting obesity, according to an article in the December issue of BioScience.
Adiponectin is a metabolic link between obesity and bone mineral density
Researchers at the University of Toronto, Faculty of Medicine, Toronto, Canada, have discovered that adiponectin, a protein secreted from adipocytes, is a metabolic link that can explain, in part, the known positive relationship between obesity and both bone mineral density and reduced susceptibility to fractures.
Sealing off portion of intestinal lining treats obesity, resolves diabetes in animal model
Lining the upper portion of the small intestine with an impermeable sleeve led to both weight loss and restoration of normal glucose metabolism in an animal model of obesity-induced diabetes.
Why women should eat less, move more and consider wearing transdermal HRT patches during menopause
Weight and appetite experts from around the world met at a conference in Bangkok earlier this year to discuss sex differences in obesity. One line of discussion looked at factors leading to women's weight gain during menopause, and how it might be avoided.
Heart patients are often not treated in accordance with guidelines
Many patients with cardiovascular disease are not given adequate drug therapy. This is the result of an international study. In the current edition of Deutsches Ärzteblatt International, Uwe Zeimer et al. present the German results of this prospective, one-year survey.
Scripps research team defines new painkilling chemical pathway
Marijuana kills pain by activating a set of proteins known as cannabinoid receptors, which can also regulate appetite, inflammation, and memory.
Researchers: Ban on fast food TV advertising would reverse childhood obesity trends
A ban on fast food advertisements in the United States could reduce the number of overweight children by as much as 18 percent, according to a new study being published this month in the Journal of Law and Economics.
Antibiotics Can Cause Pervasive, Persistent Changes to the Microbial Community in the Human Gut, MBL and Stanford Scientists Report
Using a novel technique developed by Mitchell Sogin of the Marine Biological Laboratory (MBL) to identify different types of bacteria, scientists have completed the most precise survey to date of how microbial communities in the human gut respond to antibiotic treatment.
Physical activity after bariatric surgery improves weight loss, quality of life
A new study by researchers from The Miriam Hospital's Centers for Behavioral and Preventive Medicine suggests increased physical activity after bariatric surgery can yield better postoperative outcomes.
More Obesity Current Events and Obesity News Articles
 | The Obesity Myth: Why America's Obsession with Weight is Hazardous to Your Health by Paul Campos “Campos makes his case against the “fat kills” dogma with unimpeachable evidence. The Obesity Myth should be required reading for every health professional in America. I believe any open-minded person who reads this book will conclude that we’ve been duped by a pack of self-serving lies. And we cannot get at the truth without first recognizing those lies. The Obesity Myth is a great place... |
 | Obesity Cancer & Depression: Their Common Cause & Natural Cure by F. Batmanghelidj This book, the result of over 20 years of research, looks at the conditions of obesity, cancer and depression through a new physiological perspective and offers a new approach in preventing and treating these... |
 | Exodus from Obesity: The Guide to Long-Term Success After Weight Loss Surgery by Paula F. Peck In Exodus From Obesity, Paula F. Peck provides the information, encouragement and guidelines for maintaining long-term success after weight loss surgery. Ms. Peck interweaves intelligent discussion with humorous stories about herself and individuals that have faced diet after diet and ultimately chose the gastric bypass procedure. This book is a clear, easy-to-read guide for patients, potential... |
 | Fat Politics: The Real Story behind America's Obesity Epidemic by J. Eric Oliver It seems almost daily we read newspaper articles and watch news reports exposing the growing epidemic of obesity in America. Our government tells us we are experiencing a major health crisis, with sixty percent of Americans classified as overweight, and one in four as obese. But how valid are these claims? In Fat Politics, J. Eric Oliver shows how a handful of doctors, government bureaucrats, and... |
 | Mastering Leptin: The Leptin Diet, Solving Obesity and Preventing Disease, Second Edition by Byron J. Richards, Mary Guignon Richards Mastering Leptin contains exciting health advancements in solving obesity and weight problems, fatigue and low energy, low thyroid function, hypothyroidism, stress eating and food cravings, hormonal imbalance, menopausal weight gain, accelerated aging, fibromyalgia. More than a diet book, Mastering Leptin includes lifestyle solutions that will help individuals lose weight, increase energy, and... |
 | Fed Up!: Winning the War Against Childhood Obesity by Susan Okie Obesity now ranks second only to smoking as a wholly preventable cause of death. It is a major contributor to heart disease, high blood pressure, high cholesterol, and depression. Even conservative estimates show that 20 per cent of all children are now considered to be overweight - worldwide there are 22 million kids under five years old that are defined as fat. Eating way too much unhealthy... |
 | A Parent's Guide to Childhood Obesity: A Roadmap to Health by American Academy of Pediatrics Research-based evidence informs this guide to understanding—and combating—childhood obesity. Addressing medical, emotional, and psychological factors, the sensible and tested guidelines help parents create balanced meals, encourage physical activity, and partner with pediatricians, family, schools, and child-care providers in their fight against obesity. A section on setbacks and detours... |
 | Obesity Epidemiology During the past twenty years there has been a dramatic increase in obesity in the United States. An estimated thirty percent of adults in the US are obese; in 1980, only fifteen percent were. The issue is gaining greater attention with the CDC and with the public health world in general. This book will offer practical information about the methodology of epidemiologic studies of obesity,... |
 | Cognitive-Behavioral Treatment of Obesity: A Clinician's Guide by Zafra Cooper, Christopher G. Fairburn, Deborah M. Hawker The first cognitive-behavioral treatment manual for obesity, this volume presents an innovative therapeutic model currently being evaluated in controlled research at Oxford University. From leading clinical researchers, the approach is specifically designed to overcome a major weakness of existing therapies: posttreatment weight regain. The book details powerful ways to help patients not only to... |
 | Understanding Childhood Obesity (Understanding Health and Sickness Series) by M.D., J. Clinton Smith Almost fourteen percent of American children over age six and twelve percent of adolescents are obese, more than double the rate of thirty years ago. Although there are countless diet and weight-loss books on the market, few of them explain in jargon-free terms the basic factors, the body processes that can lead to childhood obesity, and the research currently underway to combat this growing... |
| © 2008 BrightSurf.com |