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Chronic exposure to palmitate impairs fatty acid oxidation and insulin‐stimulated glucose uptake despite activation of AMPK in skeletal muscle cells
Author(s) -
Pimenta Aurelio da Silva,
Gaidhu Mandeep Pinky,
Habib Sarah,
So Mandy,
Fediuc Sergiu,
Curi Rui,
Ceddia Rolando Bacis
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.632.2
Subject(s) - ampk , medicine , endocrinology , skeletal muscle , beta oxidation , chemistry , glucose uptake , intracellular , fatty acid , palmitic acid , myogenesis , lipid metabolism , fatty acid metabolism , carbohydrate metabolism , metabolism , phosphorylation , insulin , biochemistry , biology , protein kinase a
The aim of this study was to investigate the chronic effects of palmitate on fatty acid 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 8h to 200, 400, 600, and 800uM of palmitate reduced fatty acid 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 (50–100uM) caused an increase (∼30%) in CPT‐1 activity. However, as the concentration of palmitate increased, CPT‐1 activity decreased by ∼32% after exposure for 8h to 800uM of palmitate. Although fatty acid 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 800uM palmitate, respectively. This was accompanied by a progressive and time‐dependent inhibition of glucose uptake (∼65%) in myotubes. These findings may help explain the dysfunctional adaptations that occur in glucose metabolism in skeletal muscle under conditions of chronically elevated levels of NEFAs, such as in obesity and type 2 diabetes.