Abstract
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 (WT) and streptozotocin (STZ)-induced diabetic mice. WT 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 were 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.
Highlights
Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, thereby inhibiting cholesterol biosynthesis and LDL formation with great efficacy
Myopathy was observed in both wild type (WT) and STZ muscle as a result of fluvastatin administration, no difference in the severity of myopathy was noted between WT and STZ muscle (Figure 1C)
No differences in myofiber area were noted between WT and STZ muscle as a result of fluvastatin treatment (Figure 1K)
Summary
Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, thereby inhibiting cholesterol biosynthesis and LDL formation with great efficacy. As reductions in circulating LDL cholesterol levels greatly reduce atherosclerotic cardiovascular disease (ASCVD) risk, statins are among the most widely prescribed pharmaceuticals in the world [1,2,3]. Recent reports estimate up to 25% of statin users experience some form of myopathic/ myalgia symptoms, ranging from muscle soreness to severe rhabdomyolysis [4,5,6]. Despite these concerns, the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 guidelines recommend that all diabetic individuals over the age of 40 be prescribed statins regardless of their ASCVD risk [5]
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