Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat

Abstract

The fatty acid conjugated linoleic acid (CLA) and the antioxidant R-(؉)-␣-lipoic acid (R-ALA) individually enhance glucose tolerance and insulin action on skeletal muscle glucose transport in the insulin-resistant obese Zucker rat. To date, no study has assessed the potential interactions between these 2 interventions in treating insulin resistance. The present study was designed to determine whether chronic treatment with CLA and R-ALA in combination would enhance skeletal muscle glucose transport to a greater extent than either intervention individually. CLA, R-ALA, or a combination treatment of R-ALA and CLA were administered to female obese Zucker rats for 20 days at low or high doses. Whereas low-dose R-ALA (10 mg/kg body weight) alone did not alter muscle glucose transport, low-dose CLA (0.3 g/kg) induced a significant increase (38%, P < .05) in insulin-mediated glucose transport in epitrochlearis, but not in soleus. Low-dose combination therapy brought about the greatest enhancement of insulin-mediated glucose transport in epitrochlearis (77%) and soleus (54%), with the latter effect being associated with a 50% reduction in protein carbonyls (an index of tissue oxidative stress) and a 33% diminution in muscle triglycerides. High-dose treatments with CLA (1.5 g/kg), R-ALA (50 mg/kg), and the combination of CLA and R-ALA elicited increases in insulin-mediated glucose transport in epitrochlearis (57%, 58%, and 77%) and soleus (32%, 35%, and 54%). However, whereas the individual high-dose treatments with CLA and R-ALA reduced protein carbonyls (63% and 49%) and triglycerides (29% and 28%) in soleus, no further reductions were observed with the high-dose combination treatment groups. These findings support a significant interaction between low doses of CLA and R-ALA for enhancement of insulin action on skeletal muscle glucose transport, possibly via reductions in muscle oxidative stress and in lipid storage.

Interactions of the advanced glycation end product inhibitor pyridoxamine and the antioxidant α-lipoic acid on insulin resistance in the obese Zucker rat

“…The individual effects of continuous R-ALA administration to the obese Zucker rat were consistent with our previous studies and include reductions in plasma FFA [25,35], improvements in glucose tolerance [25,35], whole-body insulin sensitivity [25,35], insulin-dependent skeletal muscle glucose transport activity [23,25,26,35], and diminution of skeletal muscle triglyceride concentrations [26,35]. The combination of the PM and R-ALA treatments resulted in substantial reductions, compared with those of the obese vehicle-treated group, of the oxidative stress biomarkers, both systemically (urine-conjugated dienes) and locally (skeletal muscle protein carbonyls).…”

Phase II enzyme induction by α-lipoic acid through phosphatidylinositol 3-kinase-dependent C/EBPs activation

“…It is now apparent that -LA modulates the intracellular redox status by quenching free radicals (Matsugo et al 1995). In the obese Zucker animal model, -LA treatment ameliorated oxidative stress (Teachey et al 2003). Thus, -LA has the ability to scavenge ROS and regenerate physiological antioxidants, thus exerting cellular protective effects against cytotoxicity.…”

Dietary conjugated linoleic acid decreases adipocyte size and favorably modifies adipokine status and insulin sensitivity in obese, insulin-resistant rats

“…Changes in skeletal muscle metabolism, including improved insulin-mediated glucose transport [18,50], greater glycogen synthase activity [50], and increased fatty acid oxidation [17,[51][52][53], have been associated with improved glucose tolerance in obese and normal-weight rats supplemented with CLA. In the present study, it is unclear whether dietary CLA affected muscle mass (ie, increased visceral adipose mass without changes in body weight may imply reduced muscle mass); however, CLA significantly reduces liver weight in this model [30].…”