EFFECT OF FATTY ACIDS ON METABOLISM IN SKELETAL MUSCLE CELLS: Randle cycle, insulin signalling and mitochondrial uncoupling

Abstract

Glucose metabolism and insulin signalling were evaluated in rat soleus muscle incubated for one hour. Electrical polarity of mitochondrial inner membrane was evaluated in cultured skeletal muscle cells. Glucose uptake was not altered by the FA: caprylic (CA), lauric, myristic, palmitic (PA), stearic (ST), oleic (OL), linoleic (LI), and eicosapentaenoic. CA, PA and ST increased the insulin-stimulated glycogen synthesis by 20%, 48% and 31%, respectively. Insulin-stimulated lactate production was decreased by CA and PA by 46% and 64%, respectively. Long-chain FA with 16 or more carbons increased glucose oxidation in the absence (59%) and presence (32%) of insulin. CA reduced glucose oxidation in the presence of the hormone (29%). PA reduced the insulin-stimulated phosphorylation of IRS-1 (24%), Akt (50%), GSK-3 (28%) and p44 and p42 MAP kinases (88%), whereas OL and LI increased the insulin-stimulated phosphorylation of IRS-1 (38%) and Akt (23%). PA increased the intracellular content of glucose-6-phosphate (27%) and citrate (13%). PA and LI decreased the electrical polarity of mitochondrial inner membrane in skeletal muscle cells in culture. The results suggest that FA, acutely, modulate skeletal muscle metabolism by Randle cycle, inhibition of insulin signalling, and mitocondrial uncoupling. Financial support: FAPESP, CNPq, and CAPES.