New clues to how the brain and body communicate to regulate weight

October 26, 2012, Beth Israel Deaconess Medical Center

Maintaining a healthy body weight may be difficult for many people, but it's reassuring to know that our brains and bodies are wired to work together to do just that—in essence, to achieve a phenomenon known as energy balance, a tight matching between the number of calories consumed versus those expended. This careful balance results from a complex interchange of neurobiological crosstalk within regions of the brain's hypothalamus, and when this "conversation" goes awry, obesity or anorexia can result.

Given the seriousness of these conditions, it's unfortunate that little is known about the details of this complex interchange. Now research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) provides new insights that help bring order to this complexity. Described in the October 26 issue of the journal Cell, the findings demonstrate how the GABA neurotransmitter selectively drives energy expenditure, and importantly, also help explain the neurocircuitry underlying the fat-burning properties of brown fat.

"Our group has built up a research program with the overall goal of unraveling the 'wiring diagram' by which the brain controls appetite and the burning of calories," says senior author Bradford Lowell, MD, PhD, a Professor of Medicine in BIDMC's Division of and Harvard Medical School. "To advance our understanding to this level, we need to know the function of specific subsets of neurons, and in addition, the upstream neurons providing input to, and the downstream neurons receiving output from, these functionally defined neurons. Until recently, such knowledge in the has been largely unobtainable."

A pearl-sized region that directs a multitude of important functions in the body, the hypothalamus is the brain's control center for . This balance results when the brain receives feedback signals from the body that communicate the status of fuel stores and then integrates this with input from the external world as well as a person's emotional state to modify feeding behavior and energy expenditure.

In this new study, the researchers investigated a unique population of neurons that are located at the base of the brain in the arcuate nucleus of the hypothalamus. "We genetically engineered mice such that they have a specific defect that prevents these neurons from releasing the inhibitory neurotransmitter, GABA," says Lowell. "Mice with this defect developed marked obesity and, remarkably, their obesity was entirely due to a defect in burning off calories," he explains, adding that food intake was entirely unaffected.

By next engineering another group of mice in which these neurons could be selectively turned on at different times, the team went on to show that the arcuate neurons act through a series of downstream neurons to drive energy expenditure in brown fat. Brown fat has been making headlines lately because many recent studies have revealed that, unlike energy-storing white fat, brown fat burns energy to generate heat. This process is called thermogenesis.

"Energy expenditure mediated by brown adipose tissue is critical in maintaining body weight and prevents diet-induced obesity. Its brain-based regulatory mechanism, however, is still poorly understood," says first author Dong Kong, PhD, an Instructor in Medicine in Lowell's laboratory. "Our discovery of a hypothalamus-based neurocircuit that ultimately controls thermogenesis is an important advance," adds Lowell. The investigators additionally found that when they turned on these neurons, energy expenditure was entirely dependent upon release of GABA. These results reveal that release of GABA from arcuate neurons selectively drives energy expenditure.

"Our findings have greatly advanced our understanding in the control of energy expenditure and have provided novel insights into the pathogenesis of obesity," says Kong.

The unique features of arcuate neurons are important because they could provide an opportunity to experimentally modify the brain's control of energy expenditure. Specifically, neurons receiving GABA-mediated signals from arcuate neurons are likely to play important roles in regulating energy expenditure, but not food intake.

"It is now important to fully delineate the upstream neurons that control these thermogenesis-regulating arcuate neurons, and also the downstream neurons that complete the 'circuit' to brown adipose tissue," Lowell adds. He and his colleagues have identified several specific types of neurons that act downstream of arcuate , but more research is needed to provide a clear and definitive diagram. Such work could uncover new opportunities for pharmacologic interventions that might lead to effective treatments for obesity and its related complications such as diabetes.

Explore further: Modulation of inhibitory output is key function of antiobesity hormone

Related Stories

Modulation of inhibitory output is key function of antiobesity hormone

July 13, 2011
Scientists have known for some time that the hormone leptin acts in the brain to prevent obesity, but the specific underlying neurocircuitry has remained a mystery. Now, new research published by Cell Press in the July 14 ...

Molecular duo dictate weight and energy levels

February 28, 2012
Yale University researchers have discovered a key cellular mechanism that may help the brain control how much we eat, what we weigh, and how much energy we have.

Treating obesity via brain glucose sensing

July 26, 2011
The past two decades have witnessed an epidemic spread of obesity-related diseases in Western countries. Elucidating the biological mechanism that links overnutrition to obesity could prove crucial in reducing obesity levels. ...

Recommended for you

Evening hours may pose higher risk for overeating, especially when under stress, study finds

January 16, 2018
Experiments with a small group of overweight men and women have added to evidence that "hunger hormone" levels rise and "satiety (or fullness) hormone" levels decrease in the evening. The findings also suggest that stress ...

Bariatric surgery prolongs lifespan in obese

January 16, 2018
Obese, middle-age men and women who had bariatric surgery have half the death rate of those who had traditional medical treatment over a 10-year period, reports a study that answers questions about the long-term risk of the ...

Sugar-sweetened drinks linked to overweight and obesity in children, adults: Analysis of new studies

December 23, 2017
A new review of the latest evidence on sugar-sweetened beverages (SSBs)- which includes 30 new studies published between 2013 and 2015 (and none of them industry sponsored) - concludes that SSB consumption is associated with ...

As income rises, women get slimmer—but not men

December 21, 2017
(HealthDay)—A comprehensive survey on the widening American waistline finds that as paychecks get bigger, women's average weight tends to drop.

Policy and early intervention can curb obesity rates

December 18, 2017
More information and emphasis on dietary lifestyle changes that prevent obesity, and its comorbidities, have not reduced the rise in obesity in U.S. adults and adolescents, according to a recent study in the New England Journal ...

Warning labels can help reduce soda consumption and obesity, new study suggests

December 15, 2017
Labels that warn people about the risks of drinking soda and other sugar-sweetened beverages can lower obesity and overweight prevalence, suggests a new Johns Hopkins Bloomberg School of Public Health study.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.