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-oxidation in skeletal muscle
1 Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA
2 Laboratory of Molecular Genetics, The Rockefeller University, New York, NY, USA
3 Division of Molecular Physiology, School of Life Sciences, Dundee University, Dundee, United Kingdom
4 Laboratory of Molecular Genetics, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
5 Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA; Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: ntambi{at}biochem.wisc.edu.
Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control point of
lipid partitioning and body weight regulation. Lack of SCD1 function increases insulin
sensitivity in skeletal muscles and significantly corrects hypometabolic phenotype of leptin-deficient
ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency. The
mechanism underlying the metabolic effects of SCD1 mutation is currently unknown. Here
we show that SCD1 deficiency reduced the total ceramide content in oxidative skeletal
muscles (soleus and red gastrocnemius) by ~40%. The mRNA levels and activity of serine
palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the
incorporation of [14C]palmitate into ceramide were decreased by ~50% in red muscles of
SCD1-/- mice. The content of fatty acyl-CoAs, which contribute to de novo ceramide
synthesis, was also reduced. The activity and mRNA levels of carnitine palmitoyltransferse
1 (CPT1) and the rate of 
-oxidation were increased in oxidative muscles of SCD1-/- mice.
Further, SCD1 deficiency increased phosphorylation of AMP-activated protein kinase
(AMPK) suggesting that AMPK activation may be partially responsible for the increased
fatty acid oxidation and decreased ceramide synthesis in red muscles of SCD1-/- mice.
SCD1 deficiency also reduced SPT activity and ceramide content, and increased AMPK
phosphorylation and CPT1 activity in muscles of ob/ob mice. Taken together, these results
indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression
and increasing rate of -oxidation in oxidative muscles.
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