ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice

Autor(es)

Zangerolamo, Lucas ^[1] ; Soares, Gabriela Moreira ^[1] ; Vettorazzi, Jean Franciesco ^[1] ; do Amaral, Maria Esmeria ^[2] ; Carneiro, Everardo Magalhaes ^[1] ; Olalla-Saad, Sara Teresinha ^[3] ; Boschero, Antonio Carlos ^[1] ; Barbosa-Sampaio, Helena Cristina ^[1]

Afiliação do(s) autor(es)

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

^[2] UNIARARAS, FHO Herminio Ometto Univ Ctr, Grad Program Biomed Sci, Araras, SP - Brazil

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

• Tipo de documento: Artigo Científico
• Fonte: Canadian Journal of Physiology and Pharmacology; v. 97, n. 11, p. 1018-1027, NOV 2019.
• Citações Web of Science: 0

Resumo

ARHGAP21 is a Rho-GAP that controls GTPases activity in several tissues, but its role on liver lipid metabolism is unknown. Thus, to achieve the Rho-GAP role in the liver, control and ARHGAP21-haplodeficient mice were fed chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD) for 12 weeks, and pyruvate and insulin tolerance tests, insulin signaling, liver glycogen and triglycerides content, gene and protein expression, and very-low-density lipoprotein secretion were measured. Het mice displayed reduced body weight and plasma triglycerides levels, and increased liver insulin signaling. Reduced gluconeogenesis and increased glycogen content were observed in Het-HFD mice. Gene and protein expression of microsomal triglyceride transfer protein were reduced in both Het mice, while the lipogenic genes SREBP-1c and ACC were increased. ARHGAP21 knockdown resulted in hepatic steatosis through increased hepatic lipogenesis activity coupled with decreases in CPT1a expression and very-low-density lipoprotein export. In conclusion, liver of ARHGAP21-haplodeficient mice are more insulin sensitive, associated with higher lipid synthesis and lower lipid export. (AU)

• Processo FAPESP: 12/14993-9 - Ativação do receptor muscarínico tipo 3 e associação com fatores de ribosilação do ADP 1 e 6 na função da célula-beta pancreática: vias de sinalização downstream, arquitetura da ilhota e secreção de insulina
• Beneficiário: Helena Cristina de Lima Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/23729-1 - Mecanismos moleculares da RhoGAP ARHGAP21 na formação de vesículas de VLDL em hepatócitos de camundongos C57BL/6 heterozigotos para ARHGAP21
• Beneficiário: Lucas Zangerolamo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático