| First Author | Zangerolamo L | Year | 2019 |
| Journal | Can J Physiol Pharmacol | Volume | 97 |
| Issue | 11 | Pages | 1018-1027 |
| PubMed ID | 31247150 | Mgi Jnum | J:343788 |
| Mgi Id | MGI:7570221 | Doi | 10.1139/cjpp-2018-0691 |
| Citation | Zangerolamo L, et al. (2019) ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice. Can J Physiol Pharmacol 97(11):1018-1027 |
| abstractText | 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. |
