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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 8
[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
Total Affiliations: 3
Document type: Journal article
Source: Canadian Journal of Physiology and Pharmacology; v. 97, n. 11, p. 1018-1027, NOV 2019.
Web of Science Citations: 0

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)

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 Sampaio
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/23729-1 - Molecular mechanisms of the ARHGAP21 RhoGAP in the VLDL vesicles formation in hepatocytes of ARHGAP21-heterozygous C57BL/6 mice
Grantee:Lucas Zangerolamo
Support type: Scholarships in Brazil - Scientific Initiation
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 type: Research Projects - Thematic Grants