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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00338

Whole-body ARHGAP21-deficiency improves energetic homeostasis in lean and obese mice

  • 1Department of Structural and Functional Biology, Institute of Biology, State University of Cam, Brazil
  • 2Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas, Brazil

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.

Keywords: ARHGAP21, Rho-GAP, energy homeostasis, food intake, Obesity

Received: 05 Dec 2018; Accepted: 10 May 2019.

Edited by:

Massimiliano Caprio, Università telematica San Raffaele, Italy

Reviewed by:

Angelo Cignarelli, University of Bari Aldo Moro, Italy
Valeria Guglielmi, Department of System Medicine, University of Rome Tor Vergata, Italy  

Copyright: © 2019 Soares, Zangerolamo, Costa Junior, Vettorazzi, Carneiro, Olalla Saad, Boschero and Barbosa Sampaio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Helena C. Barbosa Sampaio, Department of Structural and Functional Biology, Institute of Biology, State University of Cam, Campinas, Brazil, hclbarbosa@yahoo.com.br