Target for obesity drugs comes into focus

Researchers at the University of Michigan have determined how the hormone leptin, an important regulator of metabolism and body weight, interacts with a key receptor in the brain.

Leptin is a hormone secreted by fat tissue that has been of interest for researchers in obesity and Type 2 diabetes since it was discovered in 1995. Like insulin, leptin is part of a regulatory network that controls intake and expenditure of energy in the body, and a lack of leptin or resistance to it has been linked to obesity in people.

Although there can be several complex reasons behind leptin resistance, in some cases the underlying cause is malfunction of the leptin receptor in the brain. An understanding of how leptin and its receptor interact could lead to new treatments for obesity and metabolic disorders, but the structure of this signaling complex has evaded researchers for years.

Georgios Skiniotis, a faculty member at the Life Sciences Institute and assistant professor in biological chemistry at the U-M Medical School, employed electron microscopy to obtain the first picture of the interaction between leptin and its receptor.

Skiniotis also traced similarities between the leptin receptor and other receptors of the same family, which may provide insight into new targets for treatment of other hormone-related diseases.

The Obese Brain May Thwart Weight Loss

New research by Terry Davidson, director of American University’s Center for Behavioral Neuroscience, indicates that diets that lead to obesity—diets high in saturated fat and refined sugar—may cause changes to the brains of obese people that in turn may fuel overconsumption of those same foods and make weight loss more challenging.

“It is a vicious cycle that may explain why obesity is so difficult to overcome,” said Davidson, also a professor of psychology at AU.

Davidson recently published his research, “The Effects of a High-Energy Diet on Hippocampal-Dependent Discrimination Performance and Blood-Brain Barrier Integrity Differ for Diet-Induced Obese and Diet-Resistant Rats,” in the journal Physiology & Behavior.

Obesity-Related Hormone Discovered in Fruit Flies

Researchers have discovered in fruit flies a key metabolic hormone thought to be the exclusive property of vertebrates. The hormone, leptin, is a nutrient sensor, regulating energy intake and output and ultimately controlling appetite. As such, it is of keen interest to researchers investigating obesity and diabetes on the molecular level. But until now, complex mammals such as mice have been the only models for investigating the mechanisms of this critical hormone. These new findings suggest that fruit flies can provide significant insights into the molecular underpinnings of fat sensing.

“Leptin is very complex,” said Akhila Rajan, first author on the paper and a postdoctoral researcher in the lab of Norbert Perrimon, James Stillman Professor of Developmental Biology at Harvard Medical School. “These types of hormones acquire more and more complex function as they evolve. Here in the fly we’re seeing leptin in its most likely primitive form.”

New gene-therapy approach could improve obesity treatment

Medical researchers at the University of Alberta have found a new way of using gene therapy to treat obesity. The treatment was successful, resulting in less weight gain, higher activity levels and decreased insulin resistance in lab models on a high-fat, high-sugar diet.

Faculty of Medicine & Dentistry researcher Jason Dyck, who works in the Department of Pediatrics and the Department of Pharmacology, published his findings this week in the peer-reviewed journal Nutrition and Diabetes. His team found a way to deliver the obesity treatment via DNA as opposed to a virus, which has had limited success in the past, especially over the long term. The results they demonstrated corroborated findings by other researchers who conducted short-term studies or used more risky methods of gene delivery.

“I think our findings may bring this treatment one step closer to clinical trials, as this approach appears to be much safer than conventional forms of gene therapy,” said Dyck.

The obesity treatment focused on increasing levels of adiponectin, a hormone secreted from fat cells. As a person gains weight and fat cells get larger, the body secretes less of this hormone. People who are thin secrete high levels of this hormone.

“This hormone seems to be protective against a number of diseases, including diabetes and cardiovascular disease, as well as weight gain,” says Dyck. “But as you gain weight, less adiponectin is secreted and you lose the beneficial effects associated with this hormone.”

Lab animal models fed a high-fat, high-sugar diet that were given this treatment gained less weight, burned more calories, were more active, used more oxygen, and were better protected against glucose intolerance and insulin resistance than those that were fed the same diet but didn’t get the anti-obesity treatment. Dyck hopes other research teams will move his work forward.

The absence of a specific type of neuron in the brain can lead to obesity and diabetes in mice report researchers in The EMBO Journal. The outcome, however, depends on the type of diet that the animals are fed.

A lack of AgRP-neurons, brain cells known to be involved in the control of food intake, leads to obesity if mice are fed a regular carbohydrate diet. However, animals that are deficient in AgRP-neurons but which are raised on a high-fat diet are leaner and healthier. The differences are due to the influence of the AgRP-neurons on the way other tissues in the body break down and store nutrients. Mice lacking AgRP-neurons adapt poorly to a carbohydrate diet and their metabolism seems better suited for feeding on fat.

The scientists wanted to show if a primary setting in the brain might directly affect the relative balance that exists in peripheral tissue between storage, conversion and utilization of carbohydrate and lipids. “The idea that we wanted to test in our experiments was whether the action of a specific type of brain cell known as the AgRP-neuron extended beyond its known influence on food intake. We found a new function for these cells, one that affects the communication with and activities of other tissues in the body including the liver, muscle and the pancreas,” added Luquet.

The researchers showed that mice that lacked AgRP-neurons from birth and which were fed on a regular carbohydrate diet had excessive body fat, increased amounts of the sugar-regulating hormone insulin, and normal levels of glucose in the blood. When the same animals were fed a high fat diet they showed a reduced gain in body weight and improved glucose clearance in the blood.

A ‘can do’ attitude is the key to a healthy lifestyle, University of Melbourne economists have determined.

Researchers from the Melbourne Institute of Applied Economic and Social Research analysed data on the diet, exercise and personality type of more than 7,000 people. The study found those who believe their life can be changed by their own actions ate healthier food, exercised more, smoked less and avoided binge drinking.

Professor Deborah Cobb-Clark, Director of the Melbourne Institute of Applied Economic and Social Research, said those who have a greater faith in ‘luck’ or ‘fate’ are more likely to live an unhealthy life. “Our research shows a direct link between the type of personality a person has and a healthy lifestyle,“ she said.

Professor Cobb-Clark hoped the study would help inform public health policies on conditions such as obesity. “The main policy response to the obesity epidemic has been the provision of better information, but information alone is insufficient to change people’s eating habits,” she said.

“Understanding the psychological underpinning of a person’s eating patterns and exercise habits is central to understanding obesity.” The study also found men and women hold different views on the benefits of a healthy lifestyle.

Men wanted physical results from their healthy choices, while women were more receptive to the everyday enjoyment of leading a healthy lifestyle. Professor Cobb-Clarke said the research demonstrated the need for more targeted policy responses. “What works well for women may not work well for men,” she said. “Gender specific policy initiatives which respond to these objectives may be particularly helpful in promoting healthy lifestyles.”

Adequate sleep helps weight loss

Adequate sleep is an important part of a weight loss plan and should be added to the recommended mix of diet and exercise, states a commentary in CMAJ (Canadian Medical Association Journal).

Although calorie restriction and increased physical activity are recommended for weight loss, there is significant evidence that inadequate sleep is contributing to obesity. Lack of sleep increases the stimulus to consume more food and increases appetite-regulating hormones.

"The solution [to weight loss] is not as simple as ‘eat less, move more, sleep more,’" write Drs. Jean-Phillippe Chaput, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario and Angelo Tremblay, Laval University, Québec, Quebec. "However, an accumulating body of evidence suggests that sleeping habits should not be overlooked when prescribing a weight-reduction program to a patient with obesity. Sleep should be included as part of the lifestyle package that traditionally has focused on diet and physical activity."

The authors’ recently published research found that total sleep time and quality of sleep predicted the loss of fat in people enrolled in a weight loss program.

The Canadian Obesity Network has included adequate sleep in its new set of obesity management tools for physicians.

New research from the Hebrew University of Jerusalem shows that a carefully scheduled high-fat diet can lead to a reduction in body weight and a unique metabolism in which ingested fats are not stored, but rather used for energy at times when no food is available.

The results were published in FASEB Journal under the title ‘Timed high-fat diet resets circadian metabolism and prevents obesity.’

Previous research has established that disrupting mammals’ daily rhythms, or feeding them a high-fat diet, disrupts metabolism and leads to obesity. The researchers wanted to determine the effect of combining a high-fat diet with long-term feeding on a fixed schedule. They hypothesized that careful scheduling of meals would regulate the biological clock and reduce the effects of a high-fat diet that, under normal circumstances, would lead to obesity.