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老年白细胞介素-10基因敲除慢性炎症小鼠的脂肪量、代谢率和脂肪因子显著降低。

Aged interleukin-10tm1Cgn chronically inflamed mice have substantially reduced fat mass, metabolic rate, and adipokines.

作者信息

Westbrook Reyhan M, Yang Huan Le, Langdon Jackie M, Roy Cindy N, Kim Jin A, Choudhury Parichoy P, Xue Qian-Li, di Francesco Andrea, de Cabo Rafa, Walston Jeremy

机构信息

Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.

出版信息

PLoS One. 2017 Dec 21;12(12):e0186811. doi: 10.1371/journal.pone.0186811. eCollection 2017.

Abstract

Interleukin 10tm1Cgn (IL 10tm) mice have been utilized as a model of chronic inflammation and declining health span because of their propensity to develop chronic activation in NFkB pathways, skeletal muscle and cardiac changes, and mitochondrial dysfunction. We hypothesized that older IL 10tm frail mice would have alterations similar to frail, older humans in measured parameters of glucose metabolism, oxygen consumption (VO2), respiratory quotient (RQ), spontaneous locomotor activity, body composition and plasma adipokine levels. To test this hypothesis, we investigated these metabolic parameters in cohorts of 3, 10, and 20 month old IL 10tm female mice and age and gender matched C57Bl/6 mice. Insulin sensitivity, glucose homeostasis, locomotor activity and RQ were not significantly altered between the two strains of mice. Interestingly, old IL 10tm mice had significantly decreased VO2 when normalized by lean mass, but not when normalized by fat mass or the lean/fat mass ratio. NMR based body composition analysis and dissection weights show that fat mass is decreased with age in IL 10tm mice compared to controls. Further, plasma adiponectin and leptin were also decreased in IL 10tm.These findings suggest that frailty observed in this mouse model of chronic inflammation may in part be driven by alterations in fat mass, hormone secretion and energy metabolism.

摘要

白细胞介素10tm1Cgn(IL - 10tm)小鼠已被用作慢性炎症和健康寿命下降的模型,因为它们倾向于在NFkB途径中发生慢性激活、出现骨骼肌和心脏变化以及线粒体功能障碍。我们假设,年龄较大的IL - 10tm体弱小鼠在葡萄糖代谢、耗氧量(VO2)、呼吸商(RQ)、自发运动活动、身体组成和血浆脂肪因子水平的测量参数方面会有与体弱的老年人类相似的改变。为了验证这一假设,我们在3、10和20月龄的IL - 10tm雌性小鼠以及年龄和性别匹配的C57Bl/6小鼠群体中研究了这些代谢参数。两种品系小鼠之间的胰岛素敏感性、葡萄糖稳态、运动活动和RQ没有显著改变。有趣的是,按瘦体重归一化时,老年IL - 10tm小鼠的VO2显著降低,但按脂肪量或瘦/脂肪量比归一化时则没有。基于核磁共振的身体组成分析和解剖重量显示,与对照组相比,IL - 10tm小鼠的脂肪量随年龄增长而减少。此外,IL - 10tm小鼠的血浆脂联素和瘦素也降低。这些发现表明,在这种慢性炎症小鼠模型中观察到的体弱可能部分是由脂肪量、激素分泌和能量代谢的改变所驱动的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa22/5739384/b512656f3439/pone.0186811.g001.jpg

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