ω3-长链多不饱和脂肪酸改善早期过度营养导致的大鼠成年期代谢异常

Omega3-polyunsaturated fatty acid ameliorates metabolic disorders in adulthood rats caused by postnatal early overfeeding

目的探索ω3-长链多不饱和脂肪酸(ω3-PUFA)膳食干预对早期过度营养大鼠成年期白色脂肪组织线粒体功能的影响和机制。方法应用小窝鼠模型,形成营养过度组(SL组,3只/窝)或正常营养组(NL组,10只/窝),断奶后给予正常饮食或ω3-PUFA饮食(SL-FO组),喂养至13周。定期测量大鼠摄食量、体重和直肠温度,13周进行动物能量代谢监测;分别于3周、13周处死,收集皮下脂肪组织。分离小鼠腹股沟皮下前脂肪细胞诱导分化,并在分化晚期给予50μmol/L二十碳五烯酸(EPA)干预48 h。检测脂肪组织和脂肪细胞线粒体相关基因的mRNA和蛋白表达水平,以及线粒体拷贝数和细胞耗氧率。结果3周时,SL组大鼠体重、摄食量、脂肪细胞面积均大于NL组,体温低于NL组并持续到13周;13周时,SL组大鼠耗氧量、CO2产出量、产热量均低于NL组;同时3周和13周脂肪组织的线粒体功能相关基因解耦联蛋白1(UCP1)、肉毒碱棕榈酰转移酶1(CPT1)、沉默信息调节蛋白1(SIRT1)及线粒体生物合成调控基因过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)表达均显著降低(P<0.05)。断乳后ω3-PUFA膳食能减低SL大鼠体重增加,提高白色脂肪UCP1蛋白表达,恢复能量代谢水平和线粒体功能相关基因表达。体外EPA干预,脂肪细胞线粒体拷贝数增加,线粒体生物合成和功能相关基因mRNA和蛋白表达水平提高,线粒体基础耗氧率和质子漏增加(P<0.05)。结论ω3-PUFA能改善因早期过度营养而降低的大鼠皮下白色脂肪线粒体功能和生物合成,可能是鱼油膳食阻止早期过度营养程序化,恢复产热代谢的重要机制。

Objective To explore the effect and mechanism of omega 3-polyunsaturated fatty acid(ω3-PUFA)dietary intervention on mitochondrial function of white adipose tissue in adult rats with postnatal early overfeeding.Methods An overfed animal model by adjusting litter size was developed for the study of neonatal overfeeding.The litter size was adjusted to 3 male rats per litter(small litter,SL group)and 10 pups per litter(normal litter,NL group).After weaning(week 3),the pups were fed standard chow orω3-PUFA diet(SL-FO)until postnatal weeks 13.Food intake,body weight,and rectal temperature of rats were measured regularly,and energy metabolism of animals was monitored in week 13.During week 3 and 13,subcutaneous adipose tissue was collected.Inguinal preadipocytes of mice were isolated and induced to differentiate,and 50μmol/L eicosapentaenoicacid(EPA)was administered for 48 h at the late stage of differentiation.The mRNA and protein expression levels of mitochondrial related genes,mitochondrial copy number,and oxygen consumption rate of adipocytes were detected in adipose tissue and adipocytes.Results By the 3rd week,the body weight,food intake,and fat cell area in SL group were higher than those in NL group while the body temperature was lower until to 13 weeks.By the 13th week,the O2 consumption,CO2 output,and heat production of rats in SL group were lower than those in NL group.Meanwhile,the expressions of mitochondrial function related genes such as uncoupling protein 1(UCP1),carnitine palmitoyltransferase 1(CPT1),SIRT1,and mitochondrial biosynthesis regulatory gene peroxisome proliferator-activated receptor coativator-1(PGC1α)in adipose tissue by the 3rd and 13th week were significantly reduced(P<0.05).After weaning,ω3-PUFA diet significantly reduced weight gain in SL rats,increased UCP1 protein expression,restored energy metabolism level and mitochondrial function related gene expression.In vitro intervention of EPA increased the mitochondrial copy number,the mRNA and protein expression levels of mitochondrial biosynthesis and functional genes,as well as the mitochondrial basic oxygen consumption rate(P<0.05).Conclusion ω3-PUFA improves postnatal overfeeding-induced impairment of the mitochondrial function and biosynthesis of subcutaneous white adipose tissue in rats,which may be an important mechanism for fish oil diet to inhibit the early over-nutrition program and restore the thermogenic metabolism.