Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat.
The fatty acid conjugated linoleic acid (CLA) and the antioxidant R-(+)-alpha-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.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D003847:Deoxyglucose / Q000378:metabolism; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D019787:Linoleic Acid / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D000975:Antioxidants; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D008063:Thioctic Acid; D003847:Deoxyglucose; D019787:Linoleic Acid; D005947:Glucose