Role of Gq/11-alpha in metabolic regulation

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

To date we have generated mice with Gq/11-alpha deficiency in the paraventricular nucleus of the hypothalamus (PVN) using Sim1-cre transgenic mice. Findings to date show that these mice are underweight in the first month of life but then do develop severe obesity associated with hyperphagia with no change in energy expenditure. They also show a defect in the ability of a melanocortin 4 receptor (MC4R) agonist (MTII) to inhibit food intake acutely. These findings suggest that the MC4R inhibits food intake via a Gq/11-alpha pathway in the PVN. However when the mice are housed individually they do not gain weight, suggesting that environment may imppact on the phenotype. We also knocked out Gq/11-alpha in adipose tissue using aP2-cre transgenic mice and see no major phenotype, in contrast to what we see after knocking out Gs-alpha using this same cre-transgenic line (DK043316)