Elsevier

The Journal of Nutrition

Volume 140, Issue 11, November 2010, Pages 1915-1922
The Journal of Nutrition

Eicosapentaenoic Acid Prevents and Reverses Insulin Resistance in High-Fat Diet-Induced Obese Mice via Modulation of Adipose Tissue Inflammation, ,

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Abstract

We investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high saturated-fat (HF) diet-induced obesity and glucose-insulin homeostasis. Male C57BL/6J mice were fed low-fat (LF; 10% energy from fat), HF (45% energy from fat), or a HF-EPA-P (45% energy from fat; 36 g/kg EPA) diet for 11 wk. A 4th group was initially fed HF for 6 wk followed by the HF-EPA-R diet for 5 wk. As expected, mice fed the HF diet developed obesity and glucose intolerance. In contrast, mice fed the HF-EPA-P diet maintained normal glucose tolerance despite weight gain compared with the LF group. Whereas the HF group developed hyperglycemia and hyperinsulinemia, both HF-EPA groups (P and R) exhibited normal glycemia and insulinemia. Further, plasma adiponectin concentration was lower in the HF group but was comparable in the LF and HF-EPA groups, suggesting a role of EPA in preventing and improving insulin resistance induced by HF feeding. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes indicated that dietary EPA supplementation of HF diets was associated with reduced adipose inflammation and lipogenesis and elevated markers of fatty acid oxidation. In C57BL/6J mice, EPA minimized saturated fat-induced insulin resistance and this is in part mediated by its effects on fatty acid oxidation and inflammation.

Abbreviations used:

AA
arachidonic acid
AUC
area under the glucose curve
BSA
bovine serum albumin
DHA
docosahexaenoic acid
EPA
eicosapentaenoic acid
HF
high saturated fat
HF-EPA-P
high saturated fat eicosapentaenoic acid prevention
HF-EPA-R
high saturated fat eicosapentaenoic acid reversal
HOMA-IR
homeostasis model assessment of insulin resistance
IL-6
interleukin-6
LF
low fat
MCP-1
monocyte chemotactic protein-1
P
prevention
PAI-1
plasminogen activator inhibitor-1
R
reversal
TG
triglyceride

Cited by (0)

1

Supported by USDA, National Institute of Food & Agriculture-National Research Initiative award 2005-35200-15224, an AHA predoctoral fellowship, University of Tennessee Obesity Research Center and AgResearch.

2

Author disclosures: N. S. Kalupahana, K. Claycombe, S. J. Newman, T. Stewart, N. Siriwardhana, N. Matthan, A. H. Lichtenstein, and N. Moustaid-Moussa, no conflicts of interest.

3

Supplemental Figure 1 is available with the online posting of this paper at jn.nutrition.org.