Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle.

Frontiers in Endocrinology

卷:7

Alexandra N Rebalka¹  Matthew J Raleigh¹  Irena A Rebalka¹  Thomas J Hawke¹  Jonathan D Schertzer¹  Laelie A Snook²  Rebecca EK MacPherson²  David C Wright² 

[1] McMaster University;

[2] University of Guelph;

关键词: skeletal muscle;    Myopathy;    Fluvastatin;    FABPpm;    FAT/CD36;    Ectopic lipids;   

DOI  :  10.3389/fendo.2016.00095

来源: DOAJ

【 摘 要 】

While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side-effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill-defined. Here we investigate the effects of Fluvastatin treatment on muscle health in wild-type and streptozotocin (STZ)-induced diabetic mice. Wild-type and STZ-diabetic mice received diet enriched with 600 mg/kg Fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content was investigated. Our findings indicate that short-term Fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only Fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes.

【 授权许可】

Unknown