Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats.
This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.
Ghafoorunissa
Department of Biochemistry, National Institute of Nutrition, Indian Council of Medical Research, Jamai Osmania P.O., Hyderabad-500 007, A.P., India. ghafoorunissanin@yahoo.com
Ibrahim
Ahamed
A
Natarajan
Saravanan
S
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003964:Diaphragm / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D019787:Linoleic Acid / Q000008:administration & dosage; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D017962:alpha-Linolenic Acid; D013395:Sucrose; D019787:Linoleic Acid; D005947:Glucose; D009638:Norepinephrine