Low RIP140 Expression Partially Restores Metabolic Flexibility in L6 Muscle Cells Treated with High FA

Abstract

To elucidate the role of RIP140 in the regulation of fatty acid uptake (FAU) and oxidation (FAO) and glucose uptake (GU) in insulin‐resistant muscle cells, L6 myotubes were transfected with RNAi to genetically silence a control sequence (CS) or RIP140 (RIP). Cells were then incubated ± palmitic acid (FA: 400μM, 12h) to induce insulin resistance followed by incubation ± insulin (I: 1000 nM) before measurement of glucose and FA kinetics. In line with the presence of insulin resistance, FA treatment raised basal GU (122.2±5.2% vs 230.0±18.8%; P<0.05) and obliterated the I‐induced increase in GU (P<0.05). FA treatment decreased basal FAU (107.1±3.7% vs 45.4±10.5%; P<0.05) and FAO (176.8±19.6 vs 82.7±13.9%; P<0.05). I‐induced FAU and FAO was reduced by 24% (P<0.05) and 44% (P<0.05) with FA treatment. Silencing of RIP140 in FA‐treated cells did not affect basal GU or FAO but it was associated with higher FAU (45.4±10.5% vs 75.0±12.1%; P<0.05). With I stimulation, silencing of RIP140 in FA‐treated cells was associated with higher GU (29%; P<0.05), lower FAU (35%; P<0.05) and no change in FAO (P<0.05). Our data show that reduced RIP140 expression in FA‐treated muscle cells rescues insulin‐mediated GU and basal FAU but does not affect basal or I‐mediated FAO. Together, our results indicate that low RIP140 expression may partially restore insulin sensitivity when insulin resistance is induced by high FA treatment.USC Women in Science and Engineering, USC Integrative and Evolutionary Biology and USC Zumberge Research Innovation Fund