AUTHOR=Soares Gabriela Moreira , Zangerolamo Lucas , Costa-Júnior Jose Maria , Vettorazzi Jean Franciesco , Carneiro Everardo Magalhães , Saad Sara Teresinha , Boschero Antonio Carlos , Barbosa-Sampaio Helena Cristina TITLE=Whole-Body ARHGAP21-Deficiency Improves Energetic Homeostasis in Lean and Obese Mice JOURNAL=Frontiers in Endocrinology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00338 DOI=10.3389/fendo.2019.00338 ISSN=1664-2392 ABSTRACT=

Inhibition of Rab-GAP TBC1 domain family member 1 (TBC1D1) reduces body weight and increases energy expenditure in mice. Here, we assessed the possible involvement of GTPase activating protein 21 (ARHGAP21), a Rho-GAP protein, in energy homeostasis. Wild-type and whole-body ARHGAP21-haplodeficient mice were fed either chow or high-fat diet for 10 weeks. These mice were analyzed for body weight, food intake, voluntary physical activity, and energy expenditure by indirect calorimetry. Real-time PCR was performed to determine changes in the expression of hypothalamic-anorexic genes. Whole-body ARHGAP21-haplodeficient mice showed lower body weight and food intake associated with increased energy expenditure. These mice also showed higher expression of hypothalamic-anorexic genes such as POMC and CART. Our data suggest that the reduction in body weight of ARHGAP21-haplodeficient mice was related to alterations in the central nervous system. This suggests a new role for ARHGAP21 in energetic metabolism and prompts us to consider GAP protein members as possible targets for the prevention and treatment of obesity and related diseases.