Details

Autor(en) / Beteiligte

• Zangerolamo, Lucas
• Soares, Gabriela Moreira
• Vettorazzi, Jean Franciesco
• do Amaral, Maria Esméria
• Carneiro, Everardo Magalhães
• Olalla-Saad, Sara Teresinha
• Boschero, Antonio Carlos
• Barbosa-Sampaio, Helena Cristina

Titel

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

Ist Teil von

• Canadian journal of physiology and pharmacology, 2019-11, Vol.97 (11), p.1018-1027

Ort / Verlag

Canada

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.