title: Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats.
abstract: 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.
authors.affiliation: 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
authors.lastname: Ghafoorunissa
authors.forename: Ahamed
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Saravanan
authors.initials: S
authors.lastname: Natarajan
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D017962:alpha-Linolenic Acid; D013395:Sucrose; D019787:Linoleic Acid; D005947:Glucose; D009638:Norepinephrine