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標題: Palmitic acid in chicken granulosa cell death-lipotoxic mechanisms mediate reproductive inefficacy of breeder hens
作者: Y.-L.Xie
關鍵字: Broilers;Free fatty acids;Granulosa cells;Apoptosis;Lipotoxicity
Project: Theriogenology, Volume 78, Page(s) 1917–1928.
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-1 (P 0.05). Triacsin-C inhibition of fatty acyl-CoA synthesis blunted interleukin-1 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 -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.
ISSN: 0093-691X
DOI: 10.1016/j.theriogenology.2012.07.004
Appears in Collections:動物科學系

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