Recent government bans on industrial trans fatty acids (TFA) in developed countries have left naturally occurring TFA from ruminant products (e.g., dairy and beef) as the sole source of TFA in the food supply. In contrast to industrial TFA, vaccenic acid (VA; trans11-18:1), the predominant TFA isomer in ruminant products, has been associated with a reduced risk of type 2 diabetes. This study addressed the hypothesis that supplementing a high-fat diet (HFD) with VA may help to improve glucose homeostasis by activating insulin signaling molecules. Thirty-six male C57BL/6J mice (7 weeks old) were fed either a low-fat diet (LFD, 10% kcal total fat), a HFD enriched with oleic acid (OA; cis9-18:1) (HFD-OA; 45% kcal total fat, 6% kcal from OA), or a HFD enriched with VA (HFD-VA; 45% kcal total fat, 6% kcal from VA) for 19 weeks. Following the dietary intervention, the metabolic phenotype was characterized using glucose tolerance test (GTT) and insulin tolerance test (ITT). Liver tissues (4 mice per group) 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 suggest greater (P &lt; 0.01) glucose intolerance in both HFD groups compared with the LFD group (Figure 1). Conversely, our ITT data suggest that the HFD-VA group was more insulin resistant (P &lt; 0.05) compared to both LFD and HFD-OA groups. In agreement with the ITT results, we found lower (P &lt; 0.01) level of Akt phosphorylation in the liver of the HFD-VA group compared to LFD. In conclusion, this work demonstrates that contrary to our initial hypothesis, a high dose of VA (6% of calorie intake) promotes glucose intolerance and insulin resistance in HFD-fed mice. Further studies using the typical intake of VA in humans (0.5-1% of calorie intake) are required to better understand VA effects on glucose homeostasis.

Effect of trans vaccenic acid on glucose homeostasis in a mouse model of diet-induced obesity and insulin resistance

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