Change of ATP binding cassette transporter A1 and liver X receptor α expression in diabetic minipig skeletal muscle Change of LXRα/ABCA1 pathway in diabetic skeletal muscle

Abnormal high density lipoprotein (HDL) metabolism may contribute to the increased atherosclerosis associated with diabetes and insulin resistance. Cellular cholesterol efflux involves the interaction of HDL with specific receptors, such as ATP-binding cassette transporter A1 (ABCA1). Glucose may regulate ABCA1 and liver X receptor (LXR) at the transcriptional level. We examined the change of ABCA1 and LXRα expression in diabetic minipig skeletal muscle. Results showed that plasma total cholesterol, triglyceride, insulin, free fat acid (FFA), and glucose in diabetic minipigs were increased, at the end of 6 months. LXR mRNA in diabetic minpigs increases 3.0-fold and ABCA1 mRNA in diabetic minpigs increases 2.5-fold as compared with control group minpigs skeletal muscles. The results of western blotting and Immunohistochemical analyses showed that LXRα and ABCA1 protein in minpig muscles was detected and increased in diabetic minpig muscles. A marked increase in the oil red O positive-stained areas was observed in the diabetic minpigs muscles. We conclude that high fat/high sucrose (HFSD) may induce hyperglycemia, hypercholesterolemia, hyper triglyceridemia and upregulation of ABCA1 and LXRα expression in diabetic minipig skeletal muscles.