Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

Mar 14, 2013American journal of physiology. Endocrinology and metabolism

Metabolic and immune effects of n-3 fatty acids differ between gut-related and belly fat in diet-induced obese mice

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Abstract

Compared with a high-fat diet, mice on a high-fat diet enriched with long-chain n-3 polyunsaturated fatty acids showed reduced fat mass and improved metabolic health.

Mice fed a high-fat diet with long-chain n-3 polyunsaturated fatty acids exhibited smaller fat cells in mesenteric adipose tissue compared to epididymal adipose tissue.
These dietary changes resulted in improved insulin levels and lower levels of hepatic triacylglycerol and plasma non-esterified fatty acids.
Gene expression analysis indicated immune cell activation in mesenteric adipose tissue and reduced activation of intestinal endothelial cells.
Both pro-inflammatory (TNFα, MCP-1) and anti-inflammatory (IL-10) cytokines were found to be upregulated in visceral adipose tissue.
A decrease in CD4/CD8α expression was observed in mesenteric adipose tissue and the spleen, suggesting an immunosuppressive effect.

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In studies emphasizing antiobesogenic and anti-inflammatory effects of long-chain n-3 polyunsaturated fatty acids (LC-n-3 PUFA), diets with very high fat content, not well-defined fat quality, and extreme n-6/n-3 PUFA ratios have been applied frequently. Additionally, comparative analyses of visceral adipose tissues (VAT) were neglected. Considering the link of visceral obesity to insulin resistance or inflammatory bowel diseases, we hypothesized that VAT, especially mesenteric adipose tissue (MAT), may exhibit differential responsiveness to diets through modulation of metabolic and inflammatory processes. Here, we aimed to assess dietary LC-n-3 PUFA effects on MAT and epididymal adipose tissue (EAT) and on MAT-adjacent liver and intestine in diet-induced obese mice fed defined soybean/palm oil-based diets. High-fat (HF) and LC-n-3 PUFA-enriched high-fat diet (HF/n-3) contained moderately high fat with unbalanced and balanced n-6/n-3 PUFA ratios, respectively. Body composition/organ analyses, glucose tolerance test, measurements of insulin, lipids, mRNA and protein expression, and immunohistochemistry were applied. Compared with HF, HF/n-3 mice showed reduced fat mass, smaller adipocytes in MAT than EAT, improved insulin level, and lower hepatic triacylglycerol and plasma NEFA levels, consistent with liver and brown fat gene expression. Gene expression arrays pointed to immune cell activation in MAT and alleviation of intestinal endothelial cell activation. Validations demonstrated simultaneously upregulated pro- (TNFα, MCP-1) and anti-inflammatory (IL-10) cytokines and M1/M2-macrophage markers in VAT and reduced CD4/CD8α expression in MAT and spleen. Our data revealed differential responsiveness to diets for VAT through preferentially metabolic alterations in MAT and inflammatory processes in EAT. LC-n-3 PUFA effects were pro- and anti-inflammatory and disclose T cell-immunosuppressive potential.

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Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

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