Palmitic acid in chicken granulosa cell death-lipotoxic mechanisms mediate reproductive inefficacy of broiler breeder hens.
In vivo and in vitro approaches were used to elucidate mechanisms of palmitate-induced cytotoxicity of follicle granulosa cells in fuel-overloaded broiler hens. In contrast to their energy-restricted counterparts, broiler breeder hens fed ad libitum for 2 wk had dyslipidemia, atresia within hierarchical ovarian follicles, and a 34% reduction in egg production (P < 0.05). Based on vital staining of freshly isolated granulosa cells with annexin V/propidium iodide, there were increases in apoptosis consistent with suppressed Akt activation (P < 0.05). Supplementing primary granulosa cell cultures with 0.5 mM palmitate for 48 or 96 h increased apoptosis (P < 0.05). Palmitate-induced cell death was accompanied by increased acyl-CoA oxidase, carnitine palmitoyl transferase-1, serine palmitoyl transferase, and sphingomyelinase transcripts and increased concentrations of proinflammatory interleukin-1β (P < 0.05). Triacsin-C inhibition of fatty acyl-CoA synthesis blunted interleukin-1β production and rescued granulosa cultures from palmitate-induced cell death. That there was partial to complete prevention of cell death with addition of the free radical scavenger pyrrolidine dithiocarbamate, the sphingomyelinase inhibitor imipramine, or the de novo ceramide synthesis inhibitor fumonisin B1, supported the notion that palmitate-induced granulosa cell cytotoxicity operated through a palmitate-derived metabolite. Palmitoyl-CoA may be channeled into β-oxidation and/or into bioactive metabolites that increase free radical generation, an inflammatory response, and ceramide production. In conclusion, palmitate-derived metabolites activated apoptotic machinery in avian granulosa cells, which caused ovarian follicular atresia and reduced egg production in fuel-overloaded broiler breeder hens.
Department of Animal Science, National Chung Hsing University, Taichung, Taiwan.
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D000821:Animal Feed; D000822:Animal Husbandry; D000818:Animals; D001786:Blood Glucose; D015153:Blotting, Western; D016923:Cell Death; D002645:Chickens / Q000502:physiology*; D004032:Diet / Q000662:veterinary; D019587:Dietary Supplements; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000187:drug effects*; D007247:Infertility, Female / Q000139:chemically induced*; D019308:Palmitic Acid / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D014226:Triazenes / Q000633:toxicity; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014226:Triazenes; D014280:Triglycerides; D019308:Palmitic Acid; C034613:triacsin C