Hormone deficiency in brain may cause overeating

The absence of a hormone in the brain can partly be blamed for people overeating purely for pleasure, according to a new study which may lead to more targeted therapies for obesity with fewer side effects.

Researchers from Rutgers Robert Wood Johnson Medical School found that when the hormone glucagon like peptide-1 (GLP-1) was reduced in the central nervous system of laboratory mice, they overate and consumed more high fat food.

"The mice in which the GLP-1 deficiency was induced ate beyond the need for calories and showed an increased preference for high fat food," said Vincent Mirabella, a medical school and doctoral student who co-authored the study.

"Conversely when we enhanced GLP-1 signalling in the brains of mice we were able to block the preference of high fat foods," Mirabella said.

GLP-1 peptides are small sequences of amino acids that have many functions, including how our bodies regulate eating behaviours. They are secreted from cells in both the small intestine and the brain and are supposed to let our brain know when we are satisfied and should put down the fork.

Scientists said it is unclear how the GLP-1 released in the brain contributes to appetite regulation.

Although this is not the only reason why people overeat, the study provides new evidence that targeting neurons in the mesolimbic dopamine system - a reward circuit in the brain - rather than targeting the whole body might be a better way to control overeating and obesity with fewer side effects.

In the study, researchers found that activating the GLP-1 hormone in the mesolimbic system hindered communication between neurons which communicate to control reward behaviours, including eating.

The result was that mice consumed less food altogether and, more important, lost the preference for high fat food.

"These are the same areas of the brain that controls other addictive behaviours like drug and alcohol abuse and nicotine addiction," said senior-author and assistant professor Zhiping Pang.

"We believe that our work has broad implications in understanding how GLP-1 functions to influence motivational behaviours," Pang said.

Effective therapies for treating obesity are very limited. A drug that mimics the GLP-1 hormone - used first to improve glucose tolerance for those with type 2 diabetes - and recently approved by the US Food and Drug Administration is now being used as a treatment for obesity.

The injectable medication that targets the whole body, however, can possibly cause serious side effects including pancreatitis, gallbladder disease and kidney problems.

"By finding out how the central nervous system regulates food intake behaviour via GLP-1 signalling, we may be able to provide more targeted therapy with fewer side effects," Pang said.