Docosahexaenoic Acid Consumption Early in Life Improves Immune Dysfunction in High-Fat Diet-Fed Wistar Rats in a Sex-Specific Manner

Abstract

To investigate whether early-life docosahexaenoic acid (DHA) consumption mitigated the effects of a high-fat diet (HFD) on body composition, endocrine hormones, immune function, inflammatory biomarkers, and identify sex differences. Wistar rats were fed (PND 0-70) diets differing only in fat composition: control low-fat (10% fat, 0% arachidonic acid [ARA], 0% DHA), control high-fat (HF, 20% fat, 0% ARA, 0% DHA), or DHA HF (20% fat, 1% ARA, 2% DHA) (n = 16/group, males/females = 8/8). Plasma hormones (ELISA), inflammatory biomarkers (electrochemiluminescence), splenocytes phenotype (immunofluorescence), and ex vivo cytokine production (ELISA) after mitogen stimulation were measured. HFD did not alter body weight/composition or inflammatory profile but increased plasma glucagon-like peptide 1 (GLP-1, males, p = 0.02). In the spleen, HFD lowered transforming growth factor-beta (TGF-β) and increased interleukin (IL)-10 (females) and IL-2 production (p < 0.03). It also lowered % of regulatory T cells (Treg), B cells (males), conventional type 1dendritic cells (cDC1), and MHC-II and CD86 expression (males) (p < 0.03). DHA mitigated HFD-related changes in plasma GLP-1 (males) andTGF-β, IL-10 (females), and IL-2 production (p ≤ 0.03) and increased % of B cells (males), cDC1, MHC-II, and CD86 expression (males) (p < 0.03). DHA mitigated HFD-induced impaired Treg response and compromised adaptive immunity and antigen-presenting function in a sex-specific manner.

Keywords: adaptive immunity; immune response; inflammation; long‐chain polyunsaturated fatty acids; regulatory T cells.