Chronic treatment of (R)- α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats

Abstract

(R)- α -lipoic acid (ALA), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes (T2D) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D. The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D.

Keywords: (R)‐ α ‐lipoic acid; high‐fat diet; hyperglycemia; hyperlipidemia; metabolic syndrome; streptozotocin; type 2 diabetes.

Figure 1

Schematic representation of experimental protocol. ALA, Alpha lipoic acid; STZ, Streptozotocin; i.p, intraperitoneal; p.o., per oral.

Figure 2

Effect of ALA on HFD and STZ‐induced body weight change in rats. Daily recordings of the mean body weight changes of the experimental groups of rats (A) and comparison of the mean body weights of rats at weeks 0, 3, 4, and 8 among the different groups of rats (B). Treatment with ALA for 4 weeks (from week 4 to week 8) protected the diabetes‐induced weight loss (nonsignificant) as compared to diabetic control rats. Each bar represents the mean ± SEM of 5–10 rats. **P < 0.01 and ***P < 0.001 when compared with diabetic control group. NS, No significant difference between the groups in comparison.

Figure 3

Effect of ALA on high‐fat diet and STZ‐induced metabolic derangements of lipid profiles. Each bar represents the mean ± SEM of 5–10 rats. **P < 0.01 and ***P < 0.001 when compared with diabetic control group. ###P < 0.001 when compared with non‐diabetic control group. NS, No significant difference between the groups in comparison.

Figure 4

Effect of ALA on high‐fat diet and STZ‐induced atherogenic (A) and coronary risk indices (B). All bars represent Mean ± SEM of 5–10 rats (n = 5–10). ***P < 0.001 when compared with diabetic control group. ###P < 0.001 when compared with non‐diabetic control group. NS, No significant difference between the groups in comparison.