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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Sex-dependent Differences in Liver and Gut Metabolomic Profiles With Acarbose and Calorie Restriction in C57BL/6 Mice
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Sex-dependent Differences in Liver and Gut Metabolomic Profiles With Acarbose and Calorie Restriction in C57BL/6 Mice

机译:在C57BL / 6小鼠中肝脏和肠道代谢组分中的性依赖性差异

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Acarbose, an alpha-glucosidase inhibitor used in treating type 2 diabetes, impairs complex carbohydrate digestion and absorption and extends life span in mice (without a requisite reduction in food intake). To assess sex-differential effects coincident with calorie restriction versus a nonrestricted longevity enhancing intervention, we evaluated the metabolite profiles (by liquid chromatography–mass spectroscopy) from livers and cecal contents of C57BL/6J mice (n = 4/sex/group), which were maintained for 10 months under one of the three diet treatments: ad libitum control diet (CON), ad libitum control diet containing 0.1% acarbose (ACA), or 40% calorie restriction using the control diet (CR). Principal component analysis revealed sex-differential profiles with ACA in livers. Of the identified metabolites (n = 621) in liver, CR significantly altered ~44% (males:187↑/131↓, females:74↑/148↓) compared with CON, in contrast with ACA (M:165↑/61↓, F:52↑/60↓). Dissimilarity in ACA-F liver metabolites was observed for ~50% of common metabolites from ACA-M and CR-M/F. CR resulted in fewer significant cecal metabolite differences (n = 615 metabolites; M:86↑/66↓, F:51↑/48↓ vs CON), relative to ACA treatment (M:32↑/189↓, F:36↑/137↓). Metabolomic profiling identifies sex-differential and tissue-specific effects with amino acid metabolism sub-pathways including those involving tryptophan, branch-chain and sulfur amino acids, and the urea cycle, as well as bile acid, porphyrin, and cofactor metabolism pathways.
机译:Acarbose,用于治疗2型糖尿病的α-葡糖苷酶抑制剂损害复合碳水化合物消化和吸收,并延长小鼠的寿命(没有食物摄入的必要减少)。为了评估对卡路里限制与非共享寿命增强干预重合的性差异效果,我们评估了来自C57BL / 6J小鼠的肝脏和肠含量的代谢物谱(通过液相色谱 - 质谱)(n = 4 /性/组),在三种饮食治疗中保持10个月:AD Libitum Control Diet(Con),含有0.1%氨基糖(ACA)的AD Libitum控制饮食,或使用控制饮食(Cr)的40%卡路里限制。主成分分析显示了肝脏中ACA的性差分谱。在肝脏中鉴定的代谢物(n = 621),CR显着改变〜44%(男性:187↑/ 131,女性:74×/ 148↓)与孔相比,与ACA相比(M:165↑/ 61 ↓,f:52↑/ 60↓)。从ACA-M和Cr-M / F中观察到ACA-F肝脏代谢物中的常见代谢物中的差异。 CR导致较少的显着的盲肠代谢物差异(n = 615代谢物; M:86↑/ 66,f:51↑/ 48↓Vs),相对于ACA处理(M:32↑/ 189↓,f:36↑ / 137↓)。代谢组学分析识别性别差和组织特异性作用与氨基酸代谢副途径,包括那些涉及色氨酸,支链和含硫氨基酸,和尿素循环,以及胆汁酸,卟啉,和辅因子代谢途径。

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