PSI-20 Trans Vaccenic Acid Does Not Improve Insulin Resistance in Diet Induced Obese Mice

Abstract

Abstract Trans vaccenic acid (TVA, trans11-18:1) is a natural trans fatty acid that is exclusively found in ruminant fats such as dairy, beef, and lamb. Increased circulating concentrations of TVA and its metabolites are epidemiologically related to a reduced risk of insulin resistance and type 2 diabetes (T2D). However, direct causative evidence is lacking, and the mechanisms are poorly understood. The objective of this study was to evaluate whether TVA can alleviate insulin resistance in diet-induced obese mice when compared with oleic acid (OA, cis9-18:1, the major dietary cis 18:1 isomer) or trans10-18:1 (a major industrial trans fatty acid isomer). Forty-eight male C57BL/6J mice (7 weeks old) were fed either a low-fat diet (LFD,10% kcal total fat), a high-fat diet (HFD) enriched with OA (HFD-OA; 45% kcal total fat, 6% kcal from pure OA), an HFD enriched with TVA (HFD-TVA; 45% kcal total fat, 6% kcal from pure TVA), or an HFD enriched with trans-10 18:1 (HFD-T10; 45% kcal total fat, 6% kcal from pure trans-10 18:1) for 19 weeks. The metabolic phenotype was characterized using a glucose tolerance test (GTT) and insulin tolerance test (ITT). Insulin-sensitive tissues (muscle, liver, and adipose) were harvested and extracted for protein, which was analyzed for protein kinase B (Akt) and phosphorylated Akt (pAKT) by western blot using Vinculin as a loading control. The resulting band intensities were quantitated using the FluorChem 9900 program (Alpha Innotech). pAkt expression was normalized to Akt. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test. Our GTT results suggested a greater (P < 0.05) glucose intolerance in both HFD-TVA and HFD-T10 groups compared with the LFD group. Whereas HFD-OA-fed mice maintained their glucose tolerance and insulin sensitivity despite greater body weight and adiposity. In agreement with GTT and ITT results, we found reduced (P < 0.05) Akt phosphorylation in the muscle of both HFD-TVA and HFD-T10 groups compared with LFD while there was no difference in phosphorylation level in the liver and adipose. In conclusion, this work demonstrates that contrary to our initial hypothesis, a large dose of TVA (6% of calorie intake) promotes glucose intolerance and insulin resistance in HFD-fed mice. Further studies using the typical intake of TVA in humans (0.5 to 1% of calorie intake) are required to better understand the effects of TVA on glucose homeostasis.