Neural Circuit Lay Out Correlation Between Obesity and Depression

Novel neural circuit that mediates the reciprocal control of feeding and psychological states in mouse models have been identified and characterized by the researchers at Baylor College of Medicine and collaborating institutions, published in the journal Molecular Psychiatry. The findings state that obesity and mental disorders such as depression and anxiety seem to often go hand in hand. The study team investigated the neuronal circuits that could be involved in reciprocally regulating weight gain and depression or anxiety. They provided mice with a high-fat diet.

It was stated that the mice model that consumed a high-fat diet not only became obese but also anxious and depressed, a condition mediated by a defective brain circuit, as similar to human patients.

The team also showed that genetic or pharmacological correction of specific disruptions observed within the neural circuits, made the mice become less anxious and depressed followed by loss of excess body weight.

Interestingly, animals' change of food preference presented as a reason for weight loss and not due to the lack of appetite. The mice naturally preferred to eat a high-fat diet before the treatment but turned their preference toward a healthier diet with reduced fat and abundant protein and carbohydrates after the treatment.

Prevalence of Depression and Obesity

It is estimated that 43% of adults with depression are obese and adults with mental illness are more likely to develop obesity as compared to those who are mentally healthy. Hormonal dysregulation, genetic deficiency, and inflammation are among the factors that have been proposed to be involved in the connection between obesity and mental disorders.

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However the study team proved the evidence that involves neural component between the link of obesity and mental disorders. This led to the discovery that malfunctioning of two groups of brain cells – dBNST and AgRP neurons (located in separate brain areas and form a circuit or connection to each other by extending cellular projections) are responsible for development of obesity and depression in mice.

Genetic Mediators in Neural Circuit

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Genetic approaches helped identify specific genes and other mediators that were altered and mediated in the circuit's malfunction in the obese and depressed mice.

"Importantly, genetically restoring the neural defects to normal eliminated the high fat diet-induced anxiety and depression and also reduced body weight. We were surprised to see that 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", says co-first author Dr. Guobin Xia, a postdoctoral associate in the Wu lab.

"Keeping in mind translational applications of our findings to the clinic, we investigated the possibility of restoring the novel circuit pharmacologically. We discovered that the combination of two clinically-approved drugs, zonisamide and granisetron, profoundly reduced anxiety and depression in mice and promoted weight loss by synergistically acting upon two different molecular targets within our newly identified brain circuit. We consider that our results provide convincing support for further studies and future clinical trials testing the value of a cocktail therapy combining zonisamide and granisetron (or a selection of their derivatives) to treat metabolic-psychiatric diseases," says corresponding author Dr. Qi Wu, a Pew Scholar for Biomedical Sciences, Kavli Scholar and assistant professor in pediatrics-nutrition at Baylor's Children's Nutrition Research Center.

The finding reveals a key regulatory mechanism for correlating obesity and mental disorders, and also suggests the possibility of pharmacological treatment.

Source-Medindia