Role of GABAergic-Proopiomelanocortin neurons in the regulation of food intake and glycemia

TROTTA, MILAGROS; ALSINA, RAMIRO; BUMASCHNY, VIVIANA FLORENCIA

CAPITAL FEDERAL

Congreso; 2nd FALAN Congress 2016; 2016

Federation of Latin-American and Caribbean Societies for Neuroscience

Obesity is an epidemic disease that affects 600million people worldwide. Overweight arises as a consequence of an alterationin energy balance when food intake exceeds energy expenditure. Energy balanceis regulated by the nervous system, in particular, by the hypothalamus. Hypothalamicproopiomelanocortin (POMC) neurons decrease food intake and promote energyexpenditure and mutations of Pomc generesults in severe obesity, both in humans and mice. Recently, some studiesdemonstrated the existence of glutamatergic and GABAergic subpopulations ofhypothalamic POMC neurons. In order to characterize GABAergic-POMC neurons, wegenerated a reversible knockout mouse model of early-onset obesity that lacksPOMC expression in the hypothalamus. Hyperphagic knockout mice were ~60%heavier than their WT littermates but, after the rescue of Pomc exclusively in GABAergicneurons, this difference dropped to ~22% and they normalized food intake,achieving an energy balance that matches that of lean control mice. Moreover, wefound that Pomc deficiency causes glucose intolerance, not related tooverweight, which was reversed after Pomc rescue in GABAergic neurons.Surprisingly, these physiological improvements were achieved with the rescue ofonly 25% of total hypothalamic POMC neurons. Altogether, these resultsdemonstrate that GABAergic Pomc neurons have a major role in theestablishment of energy balance and glucose homeostasis.