Abstract
Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apoB transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma insulin levels after 9 and 12 months, respectively, improved intra peritoneal glucose tolerance after 6 months, and a trend towards increased insulin-stimulated glucose uptake in isolated skeletal muscle. Conclusions. The data suggests that overexpression of apoB decreases skeletal muscle lipid accumulation and attenuates peripheral insulin resistance in obese mice.
Acknowledgements
The authors thank Maria Kristensen and Karen Rasmussen for excellent technical assistance and Connie Bundgaard, Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, for language editing. The study was supported by grants from the Boserup Foundation, Copenhagen, Denmark; the Novo Nordisk Foundation, Bagsvaerd, Denmark; The Danish Diabetes Association, Odense, Denmark; and the A.P Møller Foundation for the Advancement of Medical Science, Copenhagen, Denmark.
Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.