Scd1 (stearoyl-Coenzyme A desaturase 1) is a key lipogenic enzyme regulating skeletal muscle lipid metabolism. It is expressed in nearly all tissues of humans and mice where it converts primarily stearate into oleate and, to a lesser extent, palmitate into palmitoleate. Mice lacking SCD1 expression have been shown to be resistant to the detrimental effects of high fat diets.
These transgenic animals overexpress mouse Scd1 (stearoyl-Coenzyme A desaturase 1) under the control of the human skeletal muscle-specific alpha actin promoter (ACTA1). After 8 weeks of free-wheel running, hemizygous body weights are significantly lower in exercised mice versus sedentary mice. A slight but non-significant increase in heart weight becomes significant after 4 weeks of exercise training. They display approximately 10-fold higher muscle SCD1 mRNA in soleus and gastrocnemius muscle, while brain, small intestine, liver, and lung levels remain unchanged. Diaphragm muscle mRNA expression is increased over 3,000-fold. SCD1 overexpression is associated with increased triglyceride content. Fatty acid composition of the muscle reveals a striking increase in polyunsaturated fatty acid (PUFA) content of triglycerides including linoleate. Animals display significantly increased treadmill exercise capacity, running farther and longer than wildtype mice. Hemizygous mice also exhibit decreased fasting plasma glucose, GLUT1 mRNA, fatty acid oxidation, mitochondrial content, and increased PPARG (peroxisome proliferator activated receptor gamma) and PGC1 (PPARGC1A, peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) protein expression. This strain is useful in studies of glucose and lipid metabolism in type 2 diabetes, metabolic disease and obesity.
