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Trans Fat Diet Induces Insulin Resistance in Monkeys

By Kylie Kavanagh, Kate Jones, Janet Sawyer, Kathryn Kelly, Janice D. Wagner, Lawrence L. Rudel, of the Wake Forest University School of Medicine, Winston-Salem NC. Presented on 12 June 2006 at the 66th annual scientific sessions of the American Diabetes Association.

Note: This is a research abstract. A full paper is scheduled for publication in a peer-reviewed medical journal in the near future.

Trans fatty acids (TFA) are formed during partial hydrogenation of oils. Epidemiologic evidence suggests TFA's increase cardiovascular disease and diabetes risk. We aimed to evaluate long-term consumption of a western diet (35% calories supplied as fat) with fatty acids supplied as monounsaturated cis [CIS] or as an equivalent blend of monounsaturated TFA ([TRANS] 8% of total calories, comparable to human intake estimates).

Male vervet monkeys (n=51) were fed CIS or TRANS for 5 years. Bodyweight (BW) was recorded and plasma was collected at baseline and study end for measurement of fasting glucose (GLU), insulin (INS) and fructosamine (FRU) concentrations. At study end, a subset of animals (n=9) were randomly selected for measurement of waist circumference (WAIST) and biopsy of subcutaneous fat (FAT) and skeletal muscle (MUS) before and after insulin infusion (40U/m2/min). Biopsies were analyzed for insulin receptor and AKT phosphorylation. Induced phosphorylation was calculated as indication of insulin effectiveness.

TRANS gained 7.2% of BW compared to1.8% gain in CIS (p=0.05). No differences in GLU and INS were observed however TRANS monkeys had higher FRU (mean 214 vs 168 ?mol/l; p < 0.01) which was not accounted for by BW increase. BW and WAIST was associated with INS (r=0.7, p=0.04 and r=0.85, p=0.004 respectively). Insulin stimulation of tissues indicated that diet did not effect insulin receptor phosphorylation; however, AKT phosphorylation was reduced significantly in MUS and FAT. Insulin-induced phosphorylation of MUS AKT in TRANS was nearly half that of CIS (p=0.02). Induced AKT phosphorylation in FAT of TRANS was only 15% that of CIS (p=0.1).

We conclude that in equivalent diets TFA consumption increases weight gain, which although associated with increasing INS, does not account for alterations in carbohydrate metabolism (indicated by elevated FRU). Abnormal glucose metabolism results from impaired signaling post insulin receptor binding and may reduce glucose transport in insulin sensitive tissues.

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