A fatty acid found in abundance in olive oil and other “healthy” unsaturated fats has yet another benefit: it helps keep the body satisfied to prolong the time between meals.

A new study in the October Cell Metabolism, a publication of Cell Press, reveals that once this type of fat, known as oleic acid, reaches the intestine, it is converted into a lipid hormone (oleoylethanolamide, or OEA) that wards off the next round of hunger pangs.  The researchers said it may be the first description of an ingredient in food that directly provides the raw materials for a hormone’s production.

The findings in rats may yield insight into the precise dietary makeup of fat and protein for optimal hunger control, the researchers said.  (Protein plays in important role in limiting hunger as well, but by different means.)  The newly discovered signaling pathway might also be tapped into with drugs designed to control appetite by supplementing OEA levels or blocking its breakdown.  Similarly, in conditions where people don’t eat enough, the researchers speculate that treatments targeting this system might improve the appetite.

Importantly, diets high in processed foods that are riddled with saturated fats might throw a wrench into this system of metabolic control, the researchers said.

” Eating is one of the most important things animals do,” said Daniele Piomelli of the University of California, Irvine.  “This is just one of many things that control it.  That said, a system like this could be forced to inactivation by inappropriate feeding,” he said, noting that saturated fats generally lack in oleic acid.

While such diets may lead people to overeat, Piomelli said it will also be of interest to see if this mechanism may be defective in some who tend to eat in excess.

Previous studies had shown that feeding stimulates cells in the intestinal lining to produce OEA, which, when administered as a drug, decreases meal frequency by engaging receptors called peroxisome proliferator-activated receptors a (PPARa).

Piomelli’s team now reports that infusion of fat into the small intestine stimulates the release of OEA, whereas infusion of protein or carbohydrate does not.  They also demonstrate that OEA production uses dietary oleic acid and is disrupted in mutant mice lacking the membrane fatty-acid transporter CD36.  Treatments that disrupt CD36 or PPARa undermine the hunger control otherwise driven by fat.

Overall, the results suggest that activation of small-intestinal OEA release, enabled by CD36-mediated uptake of oleic acid from the diet, serves as a molecular sensor linking fat consumption to satiety.  (Piomelli said satiety is perhaps best described as the opposite of hunger.)

” In conclusion,” the researchers wrote, “our studies identify OEA as a key physiological signal that specifically links dietary fat ingestion to across-meal satiety.  Nutritional and pharmacological strategies aimed at magnifying this lipid-sensing mechanism, such as inhibitors of OEA degradation, might be useful in the treatment of obesity and other eating disorders.”

To understand where fat comes from, you have to start with a skinny mouse.  By using such a creature, and observing the growth of fat after injections of different kinds of immature cells, scientists at the Howard Hughes Medical Institute and Rockefeller University have discovered an important fat precursor cell that may in time explain how changes in the numbers of fat cells might increase and lead to obesity.  The finding, published online in this week’s issue of the journal Cell, could also have implications for understanding how fat cells affect conditions such as diabetes and cardiovascular disease.

“The identification of white adipocyte progenitor cells provides a means for identifying factors that regulate the proliferation and differentiation of fat cells,” says senior author Jeffrey Friedman, who is the Marilyn M. Simpson Professor at Rockefeller and a Howard Hughes Medical Institute investigator.

Obesity, a major public health problem in the United States and increasingly in much of the Western world, results, in part, from an increase in the mass and number of white fat cells.  Because white fat cells are post-mitotic, meaning that they cannot divide, scientists have hypothesized that a population of fat precursor cells must exist in the fat depot in order to produce new fat cells.  But identifying these fat precursor cells has been difficult.

With the assistance of researchers in Rockefeller’s Flow Cytometry Resource Center, first author Matt Rodeheffer, a postdoctoral associate in Friedman’s Laboratory of Molecular Genetics, used a cell sorting technique called fluorescence-activated cell sorting, or FACS, to search for cell populations that could produce fat in cell cultures and identified two such populations.

To determine if these cells could develop into fat cells in living animals, Rodeheffer injected these cell populations into the fat depots of a genetically engineered mouse, developed at NIH, called fatless, which lacks white fat and mimics a condition in humans called lipodystrophy that also results in diabetes.

Rodeheffer found that only one of the isolated cell populations, which express the CD24 cell-surface marker protein, produced fat tissue in the fatless mouse.  This population normally represents only .08 percent of the non-adipocyte population in adipose tissue.

An imaging assay recently developed by co-author Kivanç Birsoy, a graduate student in Friedman’s laboratory, enabled Rodeheffer to observe the CD24-expressing cells form fat in a living animal.  Birsoy’s technique uses another animal strain called the leptin-luciferase mouse, in which the visibly detectable marker luciferase is expressed under the control of the promoter of the gene that produces the hormone leptin.  In this mouse strain the luciferase marker gene only switches on in mature fat cells, and provides a non-invasive way of watching immature fat cell precursors develop into mature fat cells in a living animal over time.

“I injected the CD24+ cells which represent a very small population of cells in normal adipose tissue into a site where the fat would normally develop in the fatless mouse, and I found that a normal sized fat depot forms at the site of injection,” says Rodeheffer.

Rodeheffer also found that the injection of the fat-producing cells corrects the fatless mouse’s diabetes, and the fat cells secrete adipocyte-specific signaling proteins called cytokines.  Both of these results confirm that the cells produced in the fatless mouse are functional fat cells.

“This finding gives us a better understanding of the basic biology of adipose tissue and opens the door for us and for other researchers to be able to study these cells in living animals and determine the molecular factors that regulate formation of adipose tissue,” says Rodeheffer.  “We then can potentially study how the growth and differentiation of these cells are regulated in obesity and determine whether or not the molecular events that are involved in the regulation of adipose tissue are contributing factors to other pathologies, such as diabetes and cardiovascular disease, that are associated with obesity and metabolic syndrome.”

When dining at Chinese Buffets, overweight individuals serve themselves and eat differently than normal weight individuals.  This may lead them to overeat, according to a recent study by Cornell University’s Food and Brand Lab.  Compared to normal weight diners, overweight individuals sat 16 feet closer to the buffet, faced the food, used larger plates, ate with forks instead of chopsticks, and served themselves immediately instead of browsing the buffet.

“What’s crazy is that these people are generally unaware of what they’re doing – they’re unaware of sitting closer, facing the food, chewing less, and so on,” say Brian Wanink, lead author of this study and of the book “Mindless Eating: Why We Eat More Than We Think.”

The study was published in the journal Obesity and includes observations of 213 diners at 11 all-you-can-eat Chinese restaurant buffets across the country.  Study participants included a range of normal weight to obese diners, none of whom were Asian.  Major study findings include:

* 27% of normal-weight patrons faced the buffet compared to 42% of obese diners.

* Overweight diners sat an average of 16 feet closer than normal-weight diners.

* 16% of obese diners sat at a booth rather than a table compared to 38% of normal weight diners

* 71% of normal-weight diners browsed the buffet before serving themselves compared to 33% of obese diners

* 24% of normal-weight people used chopsticks compared with 9% of overweight people

“When food is more convenient people tend to eat more,” say coauthor Collin R. Payne, New Mexico State University.

“These seemingly subtle differences in behavior and environment may cause people to overeat without even realizing it.”

Reported in the Oct. 3, 2008 issue of Cell, the findings–from a study in mice–point to a completely new approach to treating and preventing obesity in humans.  The discovery also offers hope for new ways to treat related disorders, such as type 2 diabetes and cardiovascular diseases–the most prevalent health problems in the United States and the rest of the developed world.

Led by Dongsheng Cai, an assistant professor of physiology at the UW School of Medicine and Public Health, the researchers looked specifically at the hypothalamus–the brain structure responsible for maintaining a steady state in the body–and for the first time found that a cell-signaling pathway primarily associated with inflammation also influences the regulation of food intake.  Stimulating the pathway led the animals to increase their energy consumption, while suppressing it helped them maintain normal food intake and body weight.

The research stems from recent explorations into the problem called metabolic inflammation, a by-product of too much food or energy consumption.  Unlike the classical inflammation typically observed in infections, injuries and diseases such as cancer, the metabolic inflammation seen in obesity-related diseases is much milder, doesn’t lead to overt symptoms or cause tissues damage.

“Metabolic inflammation is a chronic, low-grade condition consisting of inflammatory-like responses at the molecular level.  It has many downstream consequences,” says Cai.  “It causes cellular dysfunction, which can decrease the regulation of several physiological processes, including metabolism.”

Scientists believe that metabolic inflammation may be at the core of many chronic, obesity-related metabolic disorders that are so common today, he adds.

Cai and his team zeroed in on NF-kappaB, a protein complex that can be activated specifically by IKKbeta to induce inflammatory reactions in many cell systems.

In earlier studies at Harvard, Cai and colleagues found that the pathway interrupted sugar, fat or protein metabolism in tissues where metabolism typically takes place–liver, fat and skeletal muscle.  Feeding mice high-sugar and high-fat diets activated the pathway in these tissues.

Once he arrived at the SMPH three years ago, Cai began to consider whether metabolic inflammation might affect “higher-up” players in the central nervous system, particularly the hypothalamus.  This brain structure is a critical master regulator of appetite and energy balance, and also controls metabolism in the peripheral tissues he had studied before.  But nobody knew how the hypothalamus might contribute to the development of metabolic diseases such as obesity and diabetes.

“We wanted to learn whether the pathway or pathways underlying metabolic inflamm ation could affect metabolism regulators in the central nervous system,” he says.

In the current study, Cai and his team found first that IKKbeta/NF-kappaB does indeed exist in specific neurons in the hypothalamus.  The pathway is much more abundant in the hypothalamus than in peripheral tissue, and it normally remains inactive in the brain.

The researchers next showed that over-nutrition through high-fat diet feeding activates IKKbeta/NF-kappaB, specifically in neurons in the hypothalamus.

“When we knocked out the IKKbeta gene to suppress NF-kappaB activity in these neurons, the animals were significantly protected from energy over-consumption and obesity development,” Cai says.

The researchers also examined a cell component called the endoplasmic reticulum (ER), shown recently to be involved in metabolic diseases involving over-nutrition, to see if it might play a role in linking over-nutrition to activate IKKbeta/NF-kappaB in the hypothalamus.

“At the intracellular level, when the ER is challenged with over-nutrition, this leads to ER stress, which can push the IKKbeta/NF-kappaB pathway to an active state, although the involved reactions could be quite complicated,” Cai says.

In several experiments, the researchers found that ER stress caused by over-nutrition activated IKKbeta/NF-kappaB in the hypothalamus.  Suppressing ER stress in the central nervous system significantly preserved normal regulation of food intake and prevented obesity.

Cai says there’s still a lot of work to be done.  His group has begun studying IKKbeta/NF-kappaB’s connections to other pathways and regulations in the hypothalamus.

“The ultimate goal will certainly be to identify a selective and effective suppressor of the pathway to target related neurons,” he says.

But Cai continues to look at the big picture, seeking answers to questions such as: “How does the environment connect to the genetics that seem to underlie the obesity epidemic?  What are the key steps that have led to the dramatic rise of diabetes in the past three decades?  And Why can’t the body adjust to changes that have occurred in the way people eat and what they eat?”

Individuals who have a genetic mutation associated with high body mass index (BMI) may be able to offset their increased risk for obesity through physical activity, according to a report in the September 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

There is a widely acknowledged genetic component to BMI and obesity, according to background information in the article.  Recently, a strong association has been shown between BMI and variants of one gene, known as the fat mass and obesity associated (FTO) gene.  The mutations associated with obesity are present in about 30 percent of European populations and are associated with a 1.75-kilogram (about 3.9 pounds) increase in body weight.  Lifestyle factors such as diet and physical activity are also important contributors to weight gain, but it is unknown exactly how they interact with genetics.

Evadnie Rampersaud, M.S.P.H., Ph.D., then of the University of Maryland School of Medicine in Baltimore and now of the University of Miami, and colleagues analyzed DNA samples of 704 healthy Amish adults (average age 43.6, 53 percent men and 47 percent women) recruited from 2003 to 2007.  Participants also underwent a series of physiological tests, including a seven-day measurement of physical activity using an instrument known as an accelerometer.

A total of 54 percent of the men and 63.7 percent of the women were overweight, and 10.1 percent of the men and 30.5 percent of the women were obese.  In the genetic analysis, 26 single-nucleotide polymorphisms (SNPs, or changes in a single base letter of DNA) in the FTO gene were associated with BMI.

The researchers then divided participants into two groups based on their physical activity levels and assessed the relationship between BMI and the two strongest SNPs.  Both SNPs were associated with BMI only in individuals who had low physical activity scores for their age and sex; they had no effect on those with above-average physical activity scores.

“Activity levels in the ‘high-activity’ stratum were approximately 900 calories [860 calories for women and 980 calories for men] higher than in the ‘low-activity’ stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening,” the authors write.

“In conclusion, we have replicated the associations of common SNPs in the FTO gene with increased BMI and risk to obesity in the Old Order Amish,” they conclude.  “Furthermore, we provide quantitative data to show that the weight increase resulting from the presence of these SNPs is much smaller and not statistically significant in subjects who are very physically active.  This finding offers some clues to the mechanism by which FTO influences changes in BMI and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals.”

Individuals who are obese are at increased risk of many diseases, including type 2 diabetes and heart disease.  As 75%-95% of previously obese individuals regain their lost weight, many researchers are interested in developing treatments to help individuals maintain their weight loss.  A new study, by Michael Rosenbaum and colleagues, at Columbia University Medical Center, New York, has provided new insight into the critical interaction between the hormone leptin and the brain’s response to weight loss.

Leptin levels fall as obese individuals lose weight.  So, the authors set out to see whether changes in leptin levels altered activity in the regions of the brain known to have a role in regulating food intake.  They observed that activity in these regions of the brain in response to visual food-related cues changed after an obese individual successfully lost weight.  However, these changes in brain activity were not observed if the obese individual who had successfully lost weight was treated with leptin.  These data are consistent with the idea that the decrease in leptin levels that occurs when an individual loses weight serves to protect the body against the loss of body fat.  Further, both the authors and, in an accompanying commentary, Rexford Ahima, at the University of Pennsylvania School of Medicine, Philadelphia, suggest that leptin therapy after weight loss might improve weight maintenance by overriding this fat-loss defense.

Individuals who are obese are predisposed to a variety of metabolic conditions, including type 2 diabetes. A characteristic of the fat tissue (adipose tissue) of individuals who are obese is that it is inflammed, and understanding the relationship between such inflammation and the onset of the metabolic conditions is of importance in combating what has become a large public health problem. In a new mouse study, Gökhan Hotamisligil and colleagues, at the Harvard School of Public Health, Boston, found that interactions between adipocytes (fat cells) and inflammatory cells called macrophages seem to underlie the inflammation-related metabolic deterioration associated with obesity.

In the study, when adipocytes isolated from mice lacking proteins known as FABPs, which are molecules that govern metabolic and inflammatory responses, were cultured with normal macrophages, the macrophages expressed reduced levels of inflammatory molecules. Likewise, when macrophages isolated from mice lacking FABPs were cultured with normal adipocyes, the adipocytes responded more to insulin and took up more glucose. Similar results, indicating that FABPs from both adipocytes and macrophages contribute to the inflammatory basis for metabolic deterioration, were obtained in vivo. The authors therefore suggest that this FABP-related pathway may be a novel target for metabolism-related disorders.

Past research has found that patients enrolled in weight-management programs experience greater success as the frequency they meet with physicians or weight-loss counselors about their progress increases. The U.S. Preventative Services Task Force, an organization that recommends guidelines for primary care in the U.S, classifies two provider contacts with patients as intensive. A study by NiCole Keith, associate professor in the Department of Physical Education at Indiana University-Purdue University in Indianapolis, found that this current recommendation may not be intensive enough for low-income and disadvantaged populations.

Her study was conducted in an urban community health center in Indianapolis that primarily serves low-income and disadvantaged populations. The weight-management program, Take Charge Lite (TCL), was free to patients, funded by the Fairbanks Foundation and available to all patients 18 or older with a body mass index indicating they could be overweight or obese — equal to or above 25. The program was developed for English or Spanish-speaking patients and used input from physicians, administrators and patients of the clinic. If patients qualified, their physician gave them information about TCL and the program coach’s contact information. Once a patient phoned, a first visit was arranged at which the patient chose goals, weighed-in, and discussed different weight-loss strategies with the coach. Program participants could attend support groups, education or exercise classes, meet face-to-face with coaches, or have regular weigh-ins. Each of these activities qualified as a contact.

At the end of the program’s first year, the relationship between weight loss and number of contacts was evaluated. Patients with two or fewer contacts per month gained about a pound. Patients with three or four contacts per month lost about two pounds of weight and patients who had five contacts per month lost just over two pounds. Those with six or more contacts lost about five pounds and patients with more than 11 contacts per month lost about six pounds. Keith said the program will continue and that she’s optimistic about its impact. “TCL coaches helped patients find strategies tailored to patient needs and abilities to help with weight loss,” she said. “Indentifying factors associated with weight loss and program participation may improve weight loss services, maximize contact and lead to increased weight loss in this population.”

The workplace, in addition to being a place for making money, has the potential for making a dent in Americans’ struggles with obesity, according to Indiana University researchers. A study led by Whitney E. Hornsby, a graduate student in IU Bloomington’s School of Health Physical Education and Recreation, examined weight and activity levels of 56 people ages 23 to 61 who worked desk jobs. The study found that 80 percent of the employees were overweight or obese, which is higher than the general population, and the employees also reported a lower quality of life than the general population. “Obesity rates have increased while leisure time has stayed the same or increased,” said Jeanne Johnston, assistant professor in the School of HPER’s Department of Kinesiology. “We’re becoming more sedentary in our jobs. As technology improves, it makes it easier or requires us to be closer to our desks.”

• Background: The study, says Johnston, a co-author, is part of the IU researchers’ efforts to use the workplace to stimulate healthier behaviors. She said employee wellness programs typically come in two forms — they make available an on-site fitness facility that typically is rarely used, or they make available health and wellness assessments without the resources to help employees implement the recommended changes. The IU researchers are studying a behavioral change program designed to increase employees’ activity levels to the light and moderate range, rather than launching them into a full-scale workout regimen. “The transition is really important, getting to where people are in their stage of exercise and moving them along the continuum,” Johnston said. “I’m a big believer that we need to help people move from being sedentary to being active, where they can see the results. Then, they might be motivated to join a fitness facility.”