Gut bacteria linked to obesity

Researchers at the University of Maryland School of Medicine have identified 26 species of bacteria in the human gut microbiota that appear to be linked to obesity and related metabolic complications. These include insulin resistance, high blood sugar levels, increased blood pressure and high cholesterol, known collectively as "the metabolic syndrome," which significantly increases an individual’s risk of developing diabetes, cardiovascular disease and stroke.

"We identified 26 species of bacteria that were correlated with obesity and metabolic syndrome traits such as body mass index (BMI), triglycerides, cholesterol, glucose levels and C-reactive protein, a marker for inflammation," says the senior author, Claire M. Fraser, Ph.D., professor of medicine and microbiology and immunology and director of the Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine. "We can’t infer cause and effect, but it’s an important step forward that we're starting to identify bacteria that are correlated with clinical parameters, which suggests that the gut microbiota could one day be targeted with medication, diet or lifestyle changes."The results of the study, which analyzed data from the Old Order Amish in Lancaster County, Pa., are being published online on Aug. 15, 2012, in PLOS ONE, which is published by the Public Library of Science (PLOS One). The study was funded by the National Institutes of Health (NIH). (UH2/UH3 DK083982, U01 GM074518 and P30 DK072488)

Dr. Fraser says that additional research, including an interventional study with the Amish, is essential. "We can look at whether these bacteria change over time in a given individual or in response to diet or medication," she says.

Dr. Fraser notes that the research team, led by Margaret L. Zupancic, Ph.D., then a postdoctoral fellow at IGS, also found an apparent link between the gut bacteria and inflammation, which is believed to be a factor in obesity and many other chronic diseases. "This is one of the first studies of obesity in humans to make a link between inflammatory processes and specific organisms that are present in the GI tract," Dr. Fraser says, noting that participants with metabolic syndrome who had elevated serum markers associated with inflammation tended to have the lowest levels of good bacteria that have been reported previously to have anti-inflammatory properties.

The study is the result of an ongoing collaboration between Dr. Fraser and Alan R. Shuldiner, M.D., in connection with the NIH’s Human Microbiome Project, which seeks to characterize microbial communities in the body. Dr. Shuldiner, associate dean for personalized medicine and director of the Program in Personalized and Genomic Medicine at the University of Maryland School of Medicine, operates an Amish research clinic in Lancaster Pa. Over the past 20 years, he and his research team have conducted more than a dozen studies with the Amish, looking for genes that may cause common diseases, such as diabetes, osteoporosis and cardiovascular disease.

"The Old Order Amish are ideal for such studies because they are a genetically homogenous population descended from a few founder families and have a similar rural lifestyle," Dr. Shuldiner, the John L. Whitehurst Professor of Medicine, says. "We believe the results of this study are relevant to a broader population because the clinical characteristics of obesity and its complications in the Amish are no different from the general Caucasian population," he says.

E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine, says, "Obesity and its related complications have become a critical public health concern, and the number of people who are now considered obese or overweight has skyrocketed. Dr. Fraser and Dr. Shuldiner are two of our most senior research-scientists and leaders in their respective fields. This study provides valuable insights into the role the bacteria in our bodies may play in obesity and the metabolic syndrome. We may ultimately be able to target the gut microbiome to help prevent or mitigate risk factors for a number of diseases."

The researchers analyzed the bacteria in fecal samples of 310 members of the Old Order Amish community, using a process that enables them to identify a marker gene that serves as a bar code for each type of bacteria. Participants in the study ranged from lean to overweight to obese; some of the obese participants also had features of the metabolic syndrome. "Our hypothesis was that we would see a different composition in the gut microbiota in lean vs. obese individuals and possibly in individuals who were obese but also had features of the metabolic syndrome."

They discovered that every individual possessed one of three different communities of interacting bacteria, each characterized by a dominant bacterial genus. Neither BMI nor any metabolic syndrome trait was specifically associated with any of these communities. Instead, differing levels of 26 less abundant bacterial species present in all individuals appeared to be linked to obesity and certain features of the metabolic syndrome.

Interestingly, researchers also analyzed people's gut bacteria by their occupation and found that those who had regular contact with livestock, such as farmers and their wives, had bacterial communities dominated by Prevotella, a type of bacteria that is also abundant in the gut microbiota of cattle and sheep. "These findings suggest that environmental exposure may play a role in determining the composition of the gut microbiota in humans," Dr. Fraser says.

University of Maryland Medical Center (2012, August 15). Gut bacteria linked to obesity and metabolic syndrome identified. ScienceDaily. Retrieved April 26, 2013, from http://www.sciencedaily.com­/releases/2012/08/120815174902.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29

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Big Girls Don’t Cry

A study to be published in the June 2012 issue of Journal of Adolescent Health looking at the relationships between body satisfaction and healthy psychological functioning in overweight adolescents has found that young women who are happy with the size and shape of their bodies report higher levels of self-esteem. They may also be protected against the negative behavioral and psychological factors sometimes associated with being overweight.

A group of 103 overweight adolescents were surveyed between 2004 and 2006, assessing body satisfaction, weight-control behavior, importance placed on thinness, self-esteem and symptoms of anxiety and depression, among other factors.

"We found that girls with high body satisfaction had a lower likelihood of unhealthy weight-control behaviors like fasting, skipping meals or vomiting," said Kerri Boutelle, PhD, associate professor of psychiatry and pediatrics at the University of California, San Diego School of Medicine. Boutelle added that the positive relationship shown in this study between body a girl's happiness with her body and her behavioral and psychological well-being suggests that improving body satisfaction could be a key component of interventions for overweight youth.

"A focus on enhancing self-image while providing motivation and skills to engage in effect weight-control behaviors may help protect young girls from feelings of depression, anxiety or anger sometimes association with being overweight," said Boutelle.

Additional contributors included first author Taya R. Cromley, PhD, of UCLA; Stephanie Knatz and Roxanne Rockwell, UC San Diego; and Dianne Neumark-Sztainer, PhD, MPH, RD and Mary Story, PhD, RD, University of Minnesota, Minneapolis.

This study was supported by a University of Minnesota Children's Vikings Grant.

Source: University of California, San Diego Health Sciences [April 27, 2012]

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How a Single Gene Mutation Leads to Uncontrolled Obesity

Researchers at Georgetown University Medical Center have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain. What results is obesity caused by a voracious appetite. 

Their study, published March 18th on Nature Medicine's website, suggests there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating. 

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain. In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues. 

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," says the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown. 

"This discovery may open up novel strategies to help the brain control body weight," he says. 

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons. 

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them. The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice. 

Xu also found that the mice with the same Bdnf mutation grew to be severely obese. 

Other researchers began to look at the Bdnf gene in humans, and large-scale genome-wide association studies showed Bdnf gene variants are, in fact, linked to obesity. 

But, until this study, no one has been able to describe exactly how BDNF controls body weight. 

Xu's data shows that both leptin and insulin stimulate synthesis of BDNF in neuronal dendrites in order to move their chemical message from one neuron to another through synapses. The intent is to keep the leptin and insulin chemical signals moving along the neuronal highway to the correct brain locations, where the hormones will turn on a program that suppresses appetite. 

"If there is a problem with the Bdnf gene, neurons can't talk to each other, and the leptin and insulin signals are ineffective, and appetite is not modified," Xu says. 

Now that scientists know that BDNF regulates the movement of leptin and insulin signals through brain neurons, the question is whether a faulty transmission line can be repaired. 

One possible strategy would be to produce additional long-form Bdnf transcript using adeno-associated virus-based gene therapy, Xu says. But although this kind of gene therapy has proven to be safe, it is difficult to deliver across the brain blood barrier, he adds. 

"The better approach might be to find a drug that can stimulate Bdnf expression in the hypothalamus," Xu says. "We have opened the door to both new avenues in basic research and clinical therapies, which is very exciting." 

Source: Georgetown University Medical Center [March 18, 2012]

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Stressed kids more likely to become obese

The more ongoing stress children are exposed to, the greater the odds they will become obese by adolescence, reports Cornell environmental psychologist Gary Evans in the journal Pediatrics (129:1). 

Nine-year-old children who were chronically exposed to such stressors as poverty, crowded housing and family turmoil gain more weight and were significantly heavier by age 13 than they would have been otherwise, the study found. The reason, Evans and his co-authors suggest, is that ongoing stress makes it tougher for children to control their behavior and emotions -- or self-regulate. That, in turn, can lead to obesity by their teen years. 

"These children are heavier, and they gain weight faster as they grow up. A very good predictor of adults' ability to follow healthy habits is their ability to self-regulate. It seems reasonable that the origins of that are probably in childhood. This [research] is starting to lay that out," said Evans, the Elizabeth Lee Vincent Professor of Human Ecology in the Departments of Design and Environmental Analysis and of Human Development in Cornell's College of Human Ecology. 

Evans conducted the study with former students Thomas Fuller-Rowell, Ph.D. '10, now a Robert Wood Johnson postdoctoral fellow at the University of Wisconsin-Madison, and Stacey Doan, Ph.D. '10, an assistant professor of psychology at Boston University. 

The researchers measured the height and weight of 244 9-year-olds in rural New York state and calculated their various physical and psycho-social stressors -- for example, exposure to violence, living in a substandard house or having no access to such resources as books. They also measured the children's ability to delay gratification by offering them a choice between waiting for a large plate of candy versus having a medium plate immediately. The researchers measured the children's height and weight again four years later. 

While the study doesn't prove that a child's inability to delay gratification causes her to gain weight, there's strong evidence to suggest that it does, Evans said. First, previous studies have shown that chronic stress is linked to weight gain in children and teenagers, and that children eat more sugary, fatty foods when stressed. 

Second, there's a plausible neurocognitive mechanism that may help better understand this behavior, Evans said. "There's some evidence that parts of the brain that are vulnerable and sensitive to stress, particularly early in life, are some of the same parts involved in this self-regulatory behavior." 

The study has implications for education policies such as No Child Left Behind that emphasize testing cognitive abilities but ignore children's ability to control their behavior and emotions, Evans said. 

"A child's ability to self-regulate is not just predictive of things like whether you're going to have trouble with weight -- it predicts grades, graduating from high school. A 4-year-old's ability to self-regulate even predicts SAT scores. This is a very powerful phenomenon," he said. 

The findings also have implications for interventions and policies aimed at reducing individual stressors. "If it's the cumulative impact of stress on these families that is important, that means an intervention that only looks at one stressor -- say, just drug abuse, which is how most interventions are designed -- is doomed to fail," Evans concluded. 

Author: Susan Kelley | Source: Cornell University [January 21, 2012]

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When overeating, calories, not protein, contribute to increase in body fat

In a study conducted among 25 healthy individuals living in a controlled setting who were randomized to overconsumption of different levels of protein diets, those consuming the low-protein diet had less weight gain compared to those consuming normal and high protein diets, and calories alone, and not protein appeared to contribute to an increase in body fat, according to a study in the January 4 issue of JAMA. The researchers also found that protein did contribute to changes in energy expenditure and lean body mass. 

"Obesity has become a major public health concern with more than 60 percent of adults in the United States categorized as overweight and more than 30 percent as obese," according to background information in the article. The role of diet composition in response to overeating and energy dissipation is unclear. 

George A. Bray, M.D., of the Pennington Biomedical Research Center, Baton Rouge, La., and colleagues conducted a study to determine whether the level of dietary protein differentially affected body composition, weight gain, or energy expenditure under tightly controlled conditions. The randomized controlled trial included 25 U.S. healthy, weight-stable male and female volunteers, ages 18 to 35 years, with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to receive diets containing 5 percent of energy from protein (low protein), 15 percent (normal protein), or 25 percent (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40 percent more energy intake, which corresponds to 954 calories a day. 

All participants in the study gained weight and there were no differences by sex. The rate of weight gain in the low protein diet group was significantly less than in the other 2 groups (6.97 lbs. [3.16 kg] vs. 13.3 lbs [6.05 kg] for the normal protein diet group and 14.4 lbs [6.51 kg] in the high protein diet group). 

"Body fat increased similarly in all 3 protein diet groups and represented 50 percent to more than 90 percent of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet," the authors write. 

Lean body mass (body protein) decreased during the overeating period by 1.5 lbs. (0.70 kg) in the low protein diet group compared with a gain of 6.3 lbs. (2.87 kg) in the normal protein diet group and 7 lbs. (3.18 kg) in the high protein diet group. Resting energy expenditure (normal protein diet: 160 calories/day; high protein diet: 227 calories/day) increased significantly with the normal and high protein diets. 

"In summary, weight gain when eating a low protein diet (5 percent of energy from protein) was blunted compared with weight gain when eating a normal protein diet (15 percent of energy from protein) with the same number of extra calories. Calories alone, however, contributed to the increase in body fat. In contrast, protein contributed to the changes in energy expenditure and lean body mass, but not to the increase in body fat," the researchers write. 

"The key finding of this study is that calories are more important than protein while consuming excess amounts of energy with respect to increases in body fat." 

Source: JAMA and Archives Journals [January 03, 2012]

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Studies identify risk factors in rising trend of liver cancer

Doctors have known for years that the incidence of deadly liver cancer is on the rise, but what is causing that trend has remained a mystery. Two recent Mayo Clinic studies published in the January issue of Mayo Clinic Proceedings offer a clearer picture of the rise of hepatocellular carcinoma (HCC), or liver cancer, which has tripled in the U.S. in the last three decades and has a 10 to 12 percent five-year survival rate when detected in later stages.

"The studies illuminate the importance of identifying people with risk factors in certain populations to help catch the disease in its early, treatable stages," said W. Ray Kim, M.D., a specialist in Gastroenterology and Hepatology and principal investigator of one study.

Dr. Kim's research group looked at several decades of records in the Rochester Epidemiology Project, a database that accounts for an entire county's inpatient and outpatient care. The study found the overall incidence of HCC in the population (6.9 per 100,000) is higher than has been estimated for the nation based on data from the National Cancer Institute (5.1 per 100,000). The study also found that HCC, which two decades ago tended to be caused by liver-scarring diseases such as cirrhosis from alcohol consumption, is now occurring as a consequence of hepatitis C infection.

"The liver scarring from hepatitis C can take 20 to 30 years to develop into cancer," Dr. Kim says. "We're now seeing cancer patients in their 50s and 60s who contracted hepatitis C 30 years ago and didn't even know they were infected."

Eleven percent of cases were linked to obesity, in particular fatty liver disease.

"It's a small percentage of cases overall," Dr. Kim says. "But with the nationwide obesity epidemic, we believe the rates of liver cancer may dramatically increase in the foreseeable future."

Another study looked exclusively at the Somali population, which is growing in the U.S., particularly in Minnesota, where as many as 50,000 Somalis have settled in the last two decades. The East African country is known to have a high prevalence of hepatitis B, a risk factor for HCC.

Researchers investigating records in the Mayo Clinic Life Sciences System confirmed that hepatitis B remains a risk factor, but they were surprised to find that a significant percentage of liver cancer cases in the population are attributable to hepatitis C, which had not been known to be significantly prevalent.

"The study suggests that screening for hepatitis C would be helpful for the Somali population and would enable close surveillance of liver cancer among those at risk," says lead author Abdirashid Shire, Ph.D., a Mayo Clinic researcher. "That would greatly improve treatment and survival of Somalis with this type of cancer."

Source: Mayo Clinic [January 03, 2012]

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Starving orangutans might help to better understand obesity and eating disorders in humans

Rutgers Evolutionary Anthropologist Erin Vogel thinks new research published today in Biology Letters, a Journal of the Royal Society, examining how endangered Indonesian orangutans – considered a close relative to humans -- survive during times of extreme food scarcity might help scientists better understand eating disorders and obesity in humans. 

Endangered Indonesian orangutans survive during times of extreme food scarcity and starvation [Credit: Erin Vogel]

"There is such a large obesity epidemic today and yet we don't really understand the basis of the obesity condition or how these high-protein or low-protein diets work," said Vogel, whose research, Bornean orangutans on the brink of protein bankruptcy, represents the first time scientists have looked at how these long-haired, orange-colored apes -- that depend on low-protein fruit to survive -- endure protein cycling, or period bouts of protein deprivation. "I think studying the diets of some of our closest living relatives, the great apes; may help us understand issues with our own modern day diets," she said. 

According to Vogel, an assistant professor of anthropology in Department of Anthropology and Center for Human Evolutionary Studies, in the School of Arts and Sciences, the research shows that it is only during high periods of high caloric and protein intake that orangutans put on fat, a scientific fact that is sometimes ignored by those who believe that high protein, low carbohydrate diets are the best way to lose weight. She said it is only when caloric intake is restricted that orangutans use these fat reserves for energy and eventually dip into their protein (muscle) reserves – a condition that is seen with eating disorders like anorexia. 

Orangutans in particular are interesting to study, Vogel said, because they are the only documented species of non-human ape to store fat when food is abundant in the wild and use these fat reserves when preferred fruits become scarce, presumably something done by our early hominin ancestors. 

Vogel and her research team, analyzed samples collected over a five-year period to study the effects of protein recycling, which included examining urinary metabolites and nitrogen stable isotopes – compounds and byproducts in Orangutan urine. What they determined is that these primates are able to endure prolonged protein deficits without starving to death by consuming higher protein leaves and inner bark and obtaining energy from their stored body fat and even muscles for an extended period of time when low-protein fruit is unavailable. 

"We discovered through this research that the daily amount of protein the orangutans take in when fruit is not available is inadequate for humans and one-tenth of the intake of mountain gorillas. But it is sufficient to avert a severe protein deficit," said Vogel. The Bornean orangutan population has fallen drastically in the last 50 years in Indonesia to less than 55,000 and on the island of Sumatra to less than 5,000 due to a massive amount of illegal logging and further clearing of the land to develop palm oil plantations in their now impoverished rainforest habitat. Vogel says that although some palm oil companies argue that clearing partially logged areas of the rainforest for palm oil plantations is not detrimental to the existence of the orangutan because their natural habitat has already been taken away, this research on protein cycling indicates that even areas that have been partially stripped of trees are better for orangutan survival than no forest area at all. 

Source: Rutgers University [December 13, 2011]

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On track to getting even fatter

In 2020, the vast majority of adults in America will be overweight or obese and more than half will suffer from diabetes or pre-diabetic conditions, according to projections presented by Northwestern Medicine researchers at the American Heart Association (AHA) Scientific Sessions Wednesday, Nov. 16, in Orlando. 

The AHA has set a target to help Americans improve their overall heart health by 20 percent in 2020. However, if current trends continue, Americans can expect only a modest improvement of six percent in overall cardiovascular health in 2020. 

The implications of not increasing heart health by 20 percent by 2020 could be grave. Declining rates of sickness and death from cardiovascular disease may stall, and related health care costs, already projected to reach $1.1 trillion per year by 2030, could rise even further. That’s according to study author Mark Huffman, M.D., assistant professor in preventive medicine and medicine-cardiology at Northwestern University Feinberg School of Medicine and a cardiologist at Northwestern Memorial Hospital. 

Representative of all Americans, the study is based on patterns found in the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 2008. The projected numbers on weight and diabetes, based on previous trends, follow. 

• In 2020, 83 percent of men and 72 percent of women will be overweight or obese. 

• Currently, 72 percent of men and 63 percent of women are overweight or obese (people who are overweight have a Body Mass Index (BMI) of 25 to 29kg/m2, people who are obese have a BMI of 30kg/m2 or greater). 

• In 2020, 77 percent of men and 53 percent of women will have dysglycemia (either diabetes or pre-diabetes). Currently, 62 percent of men and 43 percent of women have dysglycemia. 

“To increase overall heart health by 20 percent, American adults would need to rapidly reverse these unhealthy trends -- starting today,” Huffman said. “In concert with individual choices, public health policies can be and should be effective tools to reduce smoking, increase access to healthy foods, and increase physical activity in daily life.” 

More people would need to improve health behaviors related to diet, physical activity, body weight and smoking and health factors, related to glucose, cholesterol and blood pressure. 

"We’ve been dealing with the obesity trend for the past three decades, but the impact we project on blood sugar is a true shock,” said Donald Lloyd-Jones, M.D., chair and associate professor of preventive medicine at the Feinberg School of Medicine, a physician at Northwestern Memorial Hospital and senior author of the study. “Those are some really scary numbers. When blood sugar goes up like that all of the complications of diabetes come into play." 

Less than five percent of Americans currently are considered to have ideal cardiovascular health. The modest six percent improvement in cardiovascular health that is projected for 2020 means better cholesterol and blood pressure numbers for Americans and fewer smokers. Improvements in treatment and control of cholesterol and blood pressure with medication and declines in smoking would partially account for this small boost, but they wouldn’t be enough to offset the weight and diabetes problems Americans face, Huffman said. Projected improvements in diet and physical activity also contribute to the six percent projection, but the absolute increase in Americans who consume ideal diets will remain less than two percent by 2020, if current trends continue. 

“Since the 1960s cardiovascular disease death rates have substantially decreased, but if the weight and dysglycemia trends continue to increase, we are in danger of seeing a reversal of those gains," Huffman said. 

Achieving a healthy weight through diet and physical activity is the best way most Americans can improve their cardiovascular health, but, as Huffman stressed, not smoking is the number one preventable cause of preventable death. Yet, one in five Americans still smoke. 

Author: Erin White | Source: Northwestern University [November 16, 2011]

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Childhood obesity - what are the health risks?

It is widely suspected that the current wave of obesity among children will result in greater rates of cardiovascular disease and diabetes over the next few decades. But a second systematic review of research into childhood obesity and metabolic disease in adult life has shown there is little evidence of a direct link and suggests that treating obesity during childhood will remove any risk of lasting harm. 

This new study, and the second of its kind carried out by nutrition experts at The University of Nottingham, has strengthened their original findings that we could in fact be more at risk of health problems if we are lean as children and become obese as adults. Unexpectedly the work suggests that there could even be a slight protective effect if we are overweight as children and reduce our Body Mass Index (BMI) in adulthood. 

The research, funded by the Organix Foundation, and published online in the International Journal of Obesity, warns that as a result dieticians and nutritionists are missing an important at-risk group. 

This second review has been performed by Louise Lloyd, a graduate student in nutrition, Dr Sarah McMullen, lecturer in Human Nutrition, and Professor Simon Langley-Evans, Chair in Human Nutrition, all based in the Division of Nutritional Sciences (School of Biosciences). The Division carries out research which focuses on the basis of the individual response to diet, development and ageing. 

Their review shows that previous studies suggesting that childhood obesity permanently raises risk of disease failed to take into account adult BMI. As a result, there is insufficient evidence to demonstrate links with long term-risk which are independent of adult BMI. 

The researchers reviewed 11 academic studies which considered the health of thousands of people living in westernised countries. They say that when adult BMI was accounted for, people at the lower end of BMI in childhood who became obese later in life actually had the highest chances of high blood pressure, type 2 diabetes and heart disease. 

Professor Langley-Evans said: “There is substantial evidence that childhood obesity tracks into adulthood and it is clear that adult obesity puts us at higher risk of metabolic disease. We are not therefore suggesting that childhood obesity is without consequences. Targeting childhood and adolescence for prevention and treatment of obesity is wholly appropriate in order to establish a healthy weight moving forward into the adult years.  However, we have found that the nature of the relationship between early BMI and adult disease risk is very complex. People at the lower end of the BMI range in childhood and go on to be obese as adults seem to be at particular risk. Therefore, by focusing on children who are overweight or obese for the promotion of health weight management we may be missing an important at-risk group.” 

Overweight and obesity are associated with a range of chronic diseases such as cardiovascular disease, type 2 diabetes and certain cancers. The World Health Organisation has estimated that around a third of coronary heart disease and ischaemic strike cases are attributable to excess weight. As the prevalence of excess weight and obesity continues to increase there are significant implications for population morbidity and mortality with the increase in childhood obesity of particular concern. 

Dr McMullen said: “We conducted the reviews because we were interested in the impact of obesity during childhood on long term disease risk. We were surprised to see that when we adjusted for adult body mass index the relationships disappeared and, in fact, many of them reversed. Our analysis of the research as a whole goes against many of the conclusions from the individual studies. Most surprising to us was the finding that it is those who are relatively lean in childhood but go on to be obese during adulthood who are at particular risk. 

“We must be very clear about one thing — obesity does have a very negative impact on health in many different ways. We know that people who are obese during childhood are more likely to be obese as adults, and this has a direct impact on their health and wellbeing at that time. It is generally assumed that an earlier onset and longer duration of obesity is associated with a greater cardiovascular risk, which has increased concerns about childhood obesity trends. However, very important questions remain as to the nature of the relationship. For example it isn’t clear whether weight loss interventions in adult life can fully ameliorate the risks associated with childhood obesity or whether an independent effect of childhood obesity remains, irrespective of the degree of adult weight.” 

The two reviews can be found at: 

http://www.nature.com/ijo/journal/vaop/ncurrent/full/ijo2011186a.html 

http://www.nature.com/ijo/journal/v34/n1/full/ijo200961a.html 

Source: The University of Nottingham [November 16, 2011]

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Obese monkeys lose weight on drug that attacks blood supply of fat cells

Obese rhesus monkeys lost on average 11 percent of their body weight after four weeks of treatment with an experimental drug that selectively destroys the blood supply of fat tissue, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports in Science Translational Medicine. 

Body mass index (BMI) and abdominal circumference (waistline) also were reduced, while all three measures were unchanged in untreated control monkeys. Imaging studies also showed a substantial decrease in body fat among treated animals. 

"Development of this compound for human use would provide a non-surgical way to actually reduce accumulated white fat, in contrast to current weight-loss drugs that attempt to control appetite or prevent absorption of dietary fat," said co-senior author Renata Pasqualini, Ph.D., professor in MD Anderson's David H. Koch Center for Applied Research of Genitourinary Cancers. 

Previous attempts to treat obesity have predominantly focused on drugs aimed at suppressing appetite or increasing metabolism, the researchers noted, but these efforts have been hampered by their toxic side-effects. The MD Anderson group designed a new drug, which includes a homing agent that binds to a protein on the surface of fat-supporting blood vessels and a synthetic peptide that triggers cell death. Their blood supply gone, fat cells are reabsorbed and metabolized. 

"Obesity is a major risk factor for developing cancer, roughly the equivalent of tobacco use, and both are potentially reversible" said co-senior author Wadih Arap, M.D., Ph.D., also professor in the Koch Center. "Obese cancer patients do worse in surgery, with radiation or on chemotherapy -- worse by any measure." 

Monkeys are spontaneously obese 

In earlier preclinical research, obese mice lost about 30 percent of their body weight with the drug, now called Adipotide. The drug acts on white adipose tissue, the scientific name for the unhealthy type of fat that accumulates under the skin and around the abdomen, and is a disease and mortality predictor. 

"Most drugs against obesity fail in transition between rodents and primates," Pasqualini said. "All rodent models of obesity are faulty because their metabolism and central nervous system control of appetite and satiety are very different from primates, including humans. We're greatly encouraged to see substantial weight loss in a primate model of obesity that closely matches the human condition." 

The rhesus monkeys in the current study were "spontaneously" obese, said study first author Kirstin Barnhart, D.V.M, Ph.D., a veterinary clinical pathologist at MD Anderson's Keeling Center for Comparative Medicine and Research in Bastrop, Texas. No specific actions were taken to make them overweight; they became so by overeating the same foods provided to other monkeys in the colony and avoiding physical activity. 

The wider problems of obesity 

This primate model also shares other physiological features associated with human obesity, such as metabolic syndrome, characterized by an increased resistance to insulin, which can lead to the development of type 2 diabetes and cardiovascular disease. Adipotide-treated monkeys showed marked improvements in insulin resistance –– using about 50 percent less insulin after treatment. 

Arap, Pasqualini and colleagues are preparing for a clinical trial in which obese prostate cancer patients would receive daily injections of Adipotide for 28 consecutive days. "The question is, will their prostate cancer become better if we can reduce their body weight and the associated health risks," Arap said. 

Some prostate cancer treatments, such as hormone therapy, cause weight gain. Greater weight can lead to arthritis, which in turn causes inactivity that leads to more weight gain, a cascade effect of co-morbidities, Arap said. Fat cells also secrete growth hormones that cancer cells thrive upon. 

Overall and abdominal body fat levels drop, with reversible renal side effects 

Weight, BMI and abdominal circumference all continued to drop for three weeks after treatment ended before slowly beginning to reverse during the fourth week of the follow?up period. 

Magnetic Resonance Imaging (MRI) was used to gauge abdominal body fat, thought to be the most dangerous area for humans to gain weight in terms of raising disease risk. Treated monkeys' abdominal fat levels fell by 27 percent during the study. Fat levels increased slightly in the control group. 

Lean monkeys did not lose weight in a separate study to test for potential effects of the drug in non-obese animals, indicating that the drug's effect may be selective for obese subjects. 

Monkeys in the studies remained bright and alert throughout, interacting with caretakers and demonstrating no signs of nausea or food avoidance. This is potentially an important finding since unpleasant side-effects have limited the use of approved drugs that reduce fat absorption in the intestines. 

The principal side effects were noted in the kidneys. "The renal effect was dose-dependent, predictable and reversible," Barnhart noted. 

Second drug developed via vascular ZIP codes 

This study is the second drug developed using a vascular mapping technique created by the Arap-Pasqualini lab. Blood vessels, they found, are more than a uniform and ubiquitous "pipeline" that serves the circulatory system, but differ depending on the organ or tissue that they support. 

They have developed a way of screening peptides – small bits of proteins – to identify those that bind to specific vascular cells among the many possible "ZIP codes" present in a human vascular map. For blood vessels that support fat cells, the target protein is prohibitin, which they found in unusual abundance on the blood vessel cell surface. 

"The same delivery system used in mice and monkeys was recently validated in human white fat, as reported recently by our group," Arap said. 

An earlier drug, which uses a different molecular address to target the blood supply of prostate cancer, has been evaluated in a first-in-man clinical trial, just completed at MD Anderson. 

Source: University of Texas M. D. Anderson Cancer Center [November 09, 2011]

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Study links obesity to periodontitis

In a study titled "MicroRNA Modulation in Obesity and Periodontitis," lead author Romina Perri, University of North Carolina School of Dentistry, Oral Health Institute, conducted a pilot investigation to determine whether obesity or periodontal disease modified microRNA expression and whether there was any potential interaction between obesity and periodontitis that could involve microRNA modulation. This study is published in the Journal of Dental Research, the official publication of the International and American Associations for Dental Research (IADR/AADR). 

In this investigation, total RNA was extracted from gingival biopsy samples collected from 20 patients in 4 groups (5 non-obese [BMI < 30kg/m2] participants with a healthy periodontium, 5 non-obese participants with periodontitis, 5 obese [BMI > 30kg/m2] participants with a healthy periodontium and 5 obese participants with periodontitis). 

Two microRNA species (miR-18a,miR-30e) were up-regulated among obese individuals with a healthy periodontium. Two microRNA species (miR-30e,miR-106b) were up-regulated in non-obese subjects with periodontal disease and in the presence of periodontal disease and obesity, nine microRNAs were significantly up-regulated (miR-15a,miR-18a,miR-22,miR-30d,miR-30e,miR-103,miR-106b, miR-130a,miR-142-3p,miR-185 and miR-210). The authors conclude that the data are consistent with the concept that miRNA that are induced by chronic nutritional stress leading to obesity may also non-parsimoniously modulate inflammatory pathways within periodontal tissues and affect disease expression. 

"The expression of specific microRNA species in obesity provides new insight into possible mechanisms of how risk factors might modify periodontal inflammation and may represent novel therapeutic targets," said JDR Editor-in-Chief William Giannobile. 

A perspective article titled "Obesity, Inflammation and Oral Infections: are microRNAs the Missing Link?" was co-authored by Francesco D'Aiuto and Jean Suvan, University College London Eastman Dental Institute. In it, the authors suggest that these data could represent a mechanistic breakthrough in our understanding of the modulatory effects of obesity on periodontal tissue destruction, but caution reproducibility of these findings is needed in larger and well-characterized cohorts.  

Source: International & American Associations for Dental Research [October 31, 2011]

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Obesity and depression independently increase health costs

Obesity and depression both dramatically increase health care costs, but they mainly act separately, according to a study published in the November 2011 Journal of General Internal Medicine by Group Health Research Institute scientists. Gregory Simon, MD, MPH, a Group Health psychiatrist and Group Health Research Institute senior investigator, led the research. 

“Previous research shows that both depression and obesity are associated with higher health care costs,” he said. “But depression and obesity often occur together, so it was important to know if the relationship between obesity and cost is really due to depression—or vice versa.” 

Simon and his colleagues tested whether depression confounds the increase in health care use that is associated with obesity. Confounding means an apparent connection—such as the link between increased health care costs and obesity—is influenced or even caused by a third factor. In this study, the authors tested if depression confounds the increase in health care seen in obese patients. 

The study used telephone interviews to determine obesity and depression, and Group Health’s extensive medical records to calculate health care costs for 4,462 women aged 40–65. All were enrolled in Group Health Cooperative, a nonprofit health care system in Washington and northern Idaho. Obesity was measured as body mass index (BMI), a standard obesity measure that is calculated from height and weight. A BMI below 25 is considered normal weight, 25-30 considered overweight, and over 30 is considered obese. Depression was measured with a 9-item American Psychiatric Association questionnaire. 

The researchers found: 

• In middle-aged women, health care costs increased with obesity. Specifically, costs increased 65 percent in women with a BMI of 30-35, and 157 percent in women with a BMI higher than 35, compared to women of normal weight. 

• The trend was similar for all types of health care that the researchers examined: primary care, outpatient prescriptions, specialist visits, inpatient care, and mental health care. 

• Health care costs increased with higher depression scores, but depression was a not a major confounder of the obesity results. 

• Even accounting for depression, health costs increased with every rise in BMI category. 

The study concluded that in this population of women, obesity is associated with higher health care costs, but not because of co-occurring depression. Similarly, depression is associated with higher costs, but not because of co-occurring obesity. These higher costs have an economic impact. Increased costs associated with depression were spread across all types of health care, not just mental health care. 

“Obesity and depression are both very common,” Dr. Simon said, “so the increased costs we find add up to a very large amount in the general population.” The relationships among obesity, depression, and chronic illness related to obesity are complex, as are the effects of depression on behavior and health. But one thing is clear, the study’s authors said: Effective obesity prevention is a crucial factor in tackling our rising health care costs. 

Source: Group Health Research Institute [October 31, 2011]

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