Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP-activated protein kinase in skeletal muscle cells
✍ Scribed by A.S. Pimenta; M.P. Gaidhu; S. Habib; M. So; S. Fediuc; M. Mirpourian; M. Musheev; R. Curi; R.B. Ceddia
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 180 KB
- Volume
- 217
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
The aim of this study was to investigate the chronic effects of palmitate on fatty acid (FA) oxidation, AMPK/ACC phosphorylation/activation, intracellular lipid accumulation, and the molecular mechanisms involved in these processes in skeletal muscle cells. Exposure of L6 myotubes for 8 h to 200, 400, 600, and 800 µM of palmitate did not affect cell viability but significantly reduced FA oxidation by ∼26.5%, ∼43.5%, ∼50%, and ∼47%, respectively. Interestingly, this occurred despite significant increases in AMPK (∼2.5‐fold) and ACC (∼3‐fold) phosphorylation and in malonyl‐CoA decarboxylase activity (∼38–60%). Low concentrations of palmitate (50–100 µM) caused an increase (∼30%) in CPT‐1 activity. However, as the concentration of palmitate increased, CPT‐1 activity decreased by ∼32% after exposure for 8 h to 800 µM of palmitate. Although FA uptake was reduced (∼35%) in cells exposed to increasing palmitate concentrations, intracellular lipid accumulation increased in a dose‐dependent manner, reaching values ∼2.3‐, ∼3‐, and 4‐fold higher than control in muscle cells exposed to 400, 600, and 800 µM palmitate, respectively. Interestingly, myotubes exposed to 400 µM of palmitate for 1 h increased basal glucose uptake and glycogen synthesis by ∼40%. However, as time of incubation in the presence of palmitate progressed from 1 to 8 h, these increases were abolished and a time‐dependent inhibition of insulin‐stimulated glucose uptake (∼65%) and glycogen synthesis (∼30%) was observed in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose and FA metabolism in skeletal muscle under conditions of chronically elevated circulating levels of non‐esterified FAs, such as in obesity and Type 2 Diabetes. J. Cell. Physiol. 217: 478–485, 2008. © 2008 Wiley‐Liss, Inc.