ARHGAP21 deficiency impairs hepatic lipid metabolism and improves insulin signaling in lean and obese mice
| Autor: | Maria Esmeria Corezola do Amaral, Antonio C. Boschero, Sara T. Olalla-Saad, Gabriela Moreira Soares, Jean Franciesco Vettorazzi, Helena C. Barbosa-Sampaio, Everardo M. Carneiro, Lucas Zangerolamo |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology 030209 endocrinology & metabolism GTPase Lipoproteins VLDL Liver lipid Gene Knockout Techniques Mice 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Animals Insulin Medicine Obesity Obese Mice Pharmacology biology business.industry GTPase-Activating Proteins Insulin sensitivity General Medicine Metabolism Lipid Metabolism medicine.disease Insulin receptor Glucose 030104 developmental biology Endocrinology Liver Hepatic lipid biology.protein lipids (amino acids peptides and proteins) business Glycogen Signal Transduction |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 97:1018-1027 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2018-0691 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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