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.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Zangerolamo L,Soares GM,Vettorazzi JF,do Amaral ME,Carneiro EM,Olalla-Saad ST,Boschero AC,Barbosa-Sampaio HCdoi
10.1139/cjpp-2018-0691subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1018-1027issue
11eissn
0008-4212issn
1205-7541journal_volume
97pub_type
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