How the brain and body communicate to regulate weight

Updated: Oct 27, 2012, 17:32 PM IST

Washington: In a new study, researchers have provided new insights into how our brains and bodies are wired to work together to maintain a healthy body weight.

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.

The findings by researchers from Beth Israel Deaconess Medical Center (BIDMC) 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 unravelling the ‘wiring diagram’ by which the brain controls appetite and the burning of calories,” senior author Bradford Lowell, a Professor of Medicine in BIDMC’s Division of Endocrinology and Harvard Medical School, said.

“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 hypothalamus has been largely unobtainable,” Lowell said.

A pearl-sized region that directs a multitude of important functions in the body, the hypothalamus is the brain’s control centre for energy balance.

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 behaviour 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,” Lowell said.

“Mice with this defect developed marked obesity and, remarkably, their obesity was entirely due to a defect in burning off calories,” he said.

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,” first author Dong Kong said.

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,” King added.

The study has been published in the journal Cell.