Scientists fit another piece in the weight control jigsaw puzzle

London, Aug 11 : Scientists have found a role for the GABA neurotransmitter, one of the master communicators among neurons, in the much complicated weight-control puzzle.

Headed by scientists at Beth Israel Deaconess Medical Center (BIDMC), the study may help in forming a clearer picture of the numerous events that lead to weight gain and weight loss.

"Body weight maintenance is made up of three basic stages. In the first stage, the brain receives sensory input from the body [including information provided by circulating hormones such as leptin and ghrelin and from fuels such as glucose and fatty acids," Nature magazine quoted the paper's senior author, Dr. Bradford Lowell, a Professor of Medicine at Harvard Medical School, as saying.

He said that in the second stage, the brain combine this sensory information with environmental cues (such as aromas and other enticements), as well as information gathered from the organism's emotional state.

Finally, in the last stage, the brain's neurocircuitry plays a major role by enabling the brain to make appropriate alterations in food intake and energy expenditure in order to maintain energy balance, and in turn avert weight gain and obesity.

Earlier scientists focused on identifying the neuropeptides involved in this process, which often proves essential to maintaining energy balance - but not always.

"It is well known that AgRP [Agouti-related protein] neurons play a critical role in feeding and energy balance regulation. However, the deletion of AgRP and NPY [two neuropeptides released from the AgRP neurons] produces little metabolic effect," explained Qingchun Tong, PhD, a postdoctoral fellow in the Lowell laboratory and the study's first author.

In an alternate theory, the scientists suggested that release of the GABA neurotransmitter was mediating the function of AgRP neurons.

The researchers generated a group of mice with disrupted release of GABA specifically from the AgRP neurons, and it was confirmed that genetically altered mice exhibited profound metabolic changes.

"The mice with AgRP neuron-specific disruption of GABA release were lean, had higher energy expenditure and showed resistance to diet-induced obesity. We also found that these animals showed reduced food intake response to the hormone ghrelin. This suggests to us that the neurocircuit engaging GABA release from the AgRP neurons mediates at least part of ghrelin's appetite-stimulating action," said Tong.

He added: "As these new findings demonstrate, GABA release is an important component that mediates the function of AgRP neurons. Discoveries such as this will ultimately help us to design an efficient strategy to tackle the current epidemic of obesity and metabolic disease."

The study is published in the latest on-line issue of Nature Neuroscience.

ANI