Whole-Body ARHGAP21-Deficiency Improves Energetic Homeostasis in Lean and Obese Mice

Author(s)

Soares, Gabriela Moreira ^{[1, 2]} ; Zangerolamo, Lucas ^{[1, 2]} ; Costa-Junior, Jose Maria ^{[1, 2]} ; Vettorazzi, Jean Franciesco ^{[1, 2]} ; Carneiro, Everardo Magalhaes ^{[1, 2]} ; Saad, Sara Teresinha ^[3] ; Boschero, Antonio Carlos ^{[1, 2]} ; Barbosa-Sampaio, Helena Cristina ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, UNICAMP, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Obes & Comorbid Res Ctr, UNICAMP, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, HEMOCTR, UNICAMP, Campinas, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 10, MAY 29 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 12/14993-9 - Type 3 muscarinic receptor activation and association with ADP-rybosilation factor 1 and 6 on the pancreatic beta-cell function: downstream signalling pathways, islet arquitecture and insulin secretion
• Grantee: Helena Cristina de Lima Barbosa
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
• Grantee: Antonio Carlos Boschiero
• Support Opportunities: Research Projects - Thematic Grants