Early-life dietary long-chain polyunsaturated fatty acid consumption promotes immune function and reduces systemic and adipose inflammation in a sex-specific manner in obese Wistar rats

Abstract

Long-chain polyunsaturated fatty acids (LCPUFA) promote immune development and improve obesity-related inflammation. This study determined the effects of LCPUFA-supplemented diets (age Wk3-10) fed to male and female rats on: (1) anthropometrics and glucose tolerance, (2) splenocyte membrane lipid composition, (3) systemic and intestinal immune function, and (4) systemic, subcutaneous (SAT) and visceral (VAT) adipose inflammation. Wistar rats were fed a high-fat diet (20% w/w fat) with 0% docosahexaenoic acid (DHA)+0% arachidonic acid (ARA) (control), 1% DHA+1% ARA (1% DHA), 2% DHA+1% ARA (2% DHA) or 1% DHA+1% ARA+1% eicosapentaenoic acid (EPA) (fish oil). Diets did not alter anthropometrics or glucose tolerance. Compared to control, all diets increased DHA in splenocyte phosphatidylethanolamine, 2%DHA also increased DHA in phosphatidylcholine; fish oil increased EPA in phosphatidylethanolamine and phosphatidylcholine (P < .01). Experimental diets altered splenocyte phenotypes (P < .05), including higher % of activated cytotoxic T cells (2%DHA), natural killer T cells (2%DHA, fish oil) and dendritic cells/macrophages expressing MHC-II complex (1%DHA) without altering ex vivo responses to mitogens. In mesenteric lymph nodes, experimental diets lowered IL-10 (1%DHA, 2%DHA, female-only) and increased IL-8 (2%DHA) production after mitogen stimulation (P < .01). In plasma, experimental diets lowered IL-8 (1%DHA, male-only), CRP (2%DHA) and TGF-β (2%DHA, female-only) (P < .02). In SAT, 2%DHA increased IL-10 (male-only, P < .05). In VAT, all diets increased IL-10, 2%DHA also increased leptin (P < .01). Collectively, compared to high-fat control, LCPUFA diets reduced systemic and adipose inflammation and altered the splenocyte phenotypes and MLN immune response in a sex-specific manner. These effects may indicate improved immune and adipose function and were more pronounced in rats fed the 2%DHA.

Keywords: Arachidonic acid; Cytokine production; Docosahexaenoic acid; Eicosapentaenoic acid; Mesenteric lymph nodes; Subcutaneous adipose tissue; Visceral adipose tissue.