Abstract
Dysregulated mitochondrial fatty acid oxidation in skeletal muscle occurs with overfeeding and obesity and is implicated in the development of insulin resistance. To assess the effects of eliminating mitochondrial long‐chain fatty acid oxidation on insulin sensitivity we generated mice with a muscle‐specific deficiency in Carnitine Palmitoyltransferase‐2 (Cpt2Sk−/− mice), an irreplaceable enzyme required for mitochondrial oxidation of long‐chain fatty acids.Cpt2 Sk−/− mice have lower basal glycaemia, hypo‐phosphorylation of Akt in liver and white adipose tissue with preserved Akt‐phosphorylation in muscle, and moderately increased sensitivity to glucose and insulin tolerance tests. Acute insulin stimulation increased Akt phosphorylation to similar levels in control and Cpt2 Sk−/− liver, adipose, and muscle. Thus, the induction in Akt phosphorylation from no‐insulin to insulin‐stimulated is heightened in Cpt2 Sk−/− liver and white adipose, but not in muscle.Cpt2 Sk−/− muscles are free of oxidative stress and do not accumulate lipotoxic ceramides or triacylglycerol. However, Cpt2 Sk−/− muscles, compared to controls, accumulate up to 500‐fold more long‐chain acylcarnitines. Also, Cpt2 Sk−/− muscles undergo remodeling by increasing mitochondria, fiber‐type switching, and alteration in myocyte nuclei size, number, and distribution. Taken together these data suggest that loss of muscle Cpt2 causes adaptive muscle remodeling and improves insulin sensitivity of liver and adipose, but not muscle.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Published Version
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