title: Fish oil alleviates activation of the hypothalamic-pituitary-adrenal axis associated with inhibition of TLR4 and NOD signaling pathways in weaned piglets after a lipopolysaccharide challenge.
abstract: Long-chain n-3 (ω-3) polyunsaturated fatty acids exert beneficial effects in neuroendocrine dysfunctions in animal models and clinical trials. However, the mechanism(s) underlying the beneficial effects remains to be elucidated. We hypothesized that dietary treatment with fish oil (FO) could mitigate LPS-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis through inhibition of Toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling pathways. Twenty-four weaned pigs were used in a 2 × 2 factorial design, and the main factors consisted of diet (5% corn oil vs. 5% FO) and immunological challenge (saline vs. LPS). After 21 d of dietary treatment with 5% corn oil or FO diets, pigs were treated with saline or LPS. Blood samples were collected at 0 (preinjection), 2, and 4 h postinjection, and then pigs were humanely killed by intravenous injection of 40 mg/kg body weight sodium pentobarbital for tissue sample collection. FO led to enrichment of eicosapentaenoic acid and docosahexaenoic acid and total n-3 polyunsaturated fatty acids in hypothalamus, pituitary gland, adrenal gland, spleen, and thymus. FO decreased plasma adrenocorticotrophin and cortisol concentrations as well as mRNA expressions of hypothalamic corticotropin releasing hormone and pituitary proopiomelanocortin. FO also reduced mRNA expression of tumor necrosis factor-α in hypothalamus, adrenal gland, spleen, and thymus, and of cyclooxygenase 2 in hypothalamus. Moreover, FO downregulated the mRNA expressions of Toll-like receptor 4 (TLR4) and its downstream molecules, including cluster differentiation factor 14, myeloid differentiation factor 2, myeloid differentiation factor 88, interleukin-1 receptor-associated kinase 1, tumor necrosis factor-α receptor-associated factor 6, and nuclear factor kappa-light-chain-enhancer of activated B cells p65, and also decreased the mRNA expressions of nucleotide-binding oligomerization domain 1, nucleotide-binding oligomerization domain 2, and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2. These results suggested that FO attenuates the activation of the HPA axis induced by LPS challenge. The beneficial effects of FO on the HPA axis may be associated with decreasing the production of brain or peripheral proinflammatory cytokines through inhibition of TLR4 and nucleotide-binding oligomerization domain protein signaling pathways.
authors.affiliation: Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.forename: Jack
authors.initials: J
authors.lastname: Odle
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhu
authors.forename: Dingan
authors.initials: D
authors.lastname: Pi
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.forename: Yu
authors.initials: Y
authors.lastname: Hong
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shi
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D053472:Nod Signaling Adaptor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D005395:Fish Oils; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D053472:Nod Signaling Adaptor Proteins; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; D053592:Interleukin-1 Receptor-Associated Kinases