Correcting altered brain circuit help address obesity and depression, study finds

Obesity and mental disorders such as depression and anxiety often go hand in hand, according to a new study by researchers at Baylor College of Medicine published in the journal Baylor Psychiatry.

The researchers and collaborating institutions are identifying and characterizing a novel neural circuit that mediates the reciprocal control of feeding and psychological states in mouse models. Like human patients, mice that consumed a high-fat diet not only became obese, but also anxious and depressed, a condition mediated by a defective brain circuit. When the researchers genetically or pharmacologically corrected specific disruptions they had observed within this circuit, the mice became less anxious and depressed and later lost excess body weight.

Weight loss was not the result of lack of appetite, according to the study, but of the animals' change of food preference. Before the treatment, the mice naturally preferred to eat a high-fat diet, but after the treatment they turned their preference toward a healthier diet with reduced fat and abundant protein and carbohydrates, the study said.

Reports indicate that 43 percent of adults with depression are obese and that adults with mental illness are more likely to develop obesity than those who are mentally healthy, said Qi Wu, PhD, corresponding author of the study and assistant professor in pediatrics-nutrition at Baylor's Children's Nutrition Research Center.

“Factors such as hormonal dysregulation, genetic deficiency and inflammation have been proposed to be involved in the connection between obesity and mental disorders,” said Wu in a statement. “Here we provide evidence that supports the involvement of a neural component."

To investigate the neuronal circuits that could be involved in reciprocally regulating weight gain and depression or anxiety, the researchers provided mice with a high-fat diet. As expected, the animals became obese. They also developed anxiety and depression. In these mice, the team studied the function of neuronal circuits.

The researchers discovered in normal mice that two groups of brain cells, dBNST and AgRP neurons located in separate brain areas, form a circuit or connection to each other by extending cellular projections. This newly discovered circuit was malfunctioning in mice that were both obese and depressed, the researchers said. Using genetic approaches, researchers identified specific genes and other mediators that were altered and mediated the circuit's malfunction in the obese and depressed mice.

Genetically restoring the neural defects to normal eliminated the high fat diet-induced anxiety and depression and reduced body weight. The animals lost weight, not because they lost their appetite, but because genetically aided readjustment of the mental states changed their feeding preference from high-fat to low-fat food.

The researchers said the discovery opens doors to potential treatment options.