ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice.
Can J Physiol Pharmacol
; 97(11): 1018-1027, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31247150
ABSTRACT
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.
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MEDLINE
Assunto principal:
Proteínas Ativadoras de GTPase
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Metabolismo dos Lipídeos
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Técnicas de Inativação de Genes
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Insulina
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Fígado
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Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article