Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice.
Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice.
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DOI：
10.1111/j.1474-9726.2010.00648.x
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发表时间：
2011-02
期刊：
影响因子：
7.8
通讯作者：
Klaus S
中科院分区：
文献类型：
--
作者：
Keipert S;Voigt A;Klaus S
在随意喂养的情况下，饮食和能量代谢是如何相互作用决定寿命的，目前知之甚少。从12周龄到死亡，骨骼肌线粒体解偶联增加的雄性和雌性野生型(WT)和转基因(TG)小鼠(HSA-mUCP1小鼠)被喂以三种不同的半合成饲料中的一种：对照组(高碳水化合物/低脂肪-HCLF)和两种高脂肪饲料：高碳水化合物/高脂肪(HCHF)和低碳水化合物/高脂肪(LCHF)。与对照组和LCHF组相比，高脂饮食组大鼠摄食速度快，体脂含量显著增加。与HCLF相比，WT的中位寿命分别减少33%(HCHF)和7%(LCHF)。从24周开始，与对照组相比，西药组胰岛素抵抗(HOMA)显著增加。与WT相比，TG小鼠瘦体重较低，能量消耗、胰岛素敏感性和最长寿命(+10%)增加。他们在HCHF上表现出肥胖的延迟发展，但达到了与WT相似的最大肥胖率。与对照组相比，甘油三酯的中位寿命仅轻微缩短(−为7%)，且不受左心衰的影响。相关分析表明，寿命缩短与高增脂率的关系比与肥胖本身的关系更强。此外，胰岛素抵抗与寿命呈负相关，体重比能量消耗与寿命呈正相关。我们得出的结论是：(I)饮食中的大量营养素比例强烈影响肥胖的发展、血糖稳态和寿命，(Ii)骨骼肌线粒体解偶联减轻了高脂饮食的有害影响，以及(Iii)早期能量稳态失衡导致的胰岛素抵抗增加预示着寿命的缩短。
Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisynthetic diets differing in macronutrient ratio: control (high-carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat (HCHF), and low-carbohydrate/high-fat (LCHF). Compared to control and LCHF, HCHF feeding rapidly and significantly increased body fat content in WT. Median lifespan of WT was decreased by 33% (HCHF) and 7% (LCHF) compared to HCLF. HCHF significantly increased insulin resistance (HOMA) of WT from 24 weeks on compared to control. TG mice had lower lean body mass and increased energy expenditure, insulin sensitivity, and maximum lifespan (+10%) compared to WT. They showed a delayed development of obesity on HCHF but reached similar maximum adiposity as WT. TG median lifespan was only slightly reduced by HCHF (−7%) and unaffected by LCHF compared to control. Correlation analyses showed that decreased longevity was more strongly linked to a high rate of fat gain than to adiposity itself. Furthermore, insulin resistance was negatively and weight-specific energy expenditure was positively correlated with longevity. We conclude that (i) dietary macronutrient ratios strongly affected obesity development, glucose homeostasis, and longevity, (ii) that skeletal muscle mitochondrial uncoupling alleviated the detrimental effects of high-fat diets, and (iii) that early imbalances in energy homeostasis leading to increased insulin resistance are predictive for a decreased lifespan.
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影响因子：
4.6
作者：
Katterle, Yvonne;Keipert, Susanne;Klaus, Susanne
通讯作者：
Klaus, Susanne
DOI：
10.1161/01.atv.0000019404.65403.71
发表时间：
2002-06-01
影响因子：
8.7
作者：
Bernal-Mizrachi, C;Weng, S;Semenkovich, CF
通讯作者：
Semenkovich, CF
影响因子：
5.3
作者：
Flurkey, K;Papaconstantinou, J;Harrison, DE
通讯作者：
Harrison, DE
DOI：
10.1093/gerona/glp175
发表时间：
2010-01-01
影响因子：
5.1
作者：
Berryman, Darlene E.;List, Edward O.;Kopchick, John J.
通讯作者：
Kopchick, John J.
DOI：
10.18632/aging.100132
发表时间：
2010-03
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV;Campisi J;Sinclair DA;Bartke A;Blasco MA;Bonner WM;Bohr VA;Brosh RM Jr;Brunet A;Depinho RA;Donehower LA;Finch CE;Finkel T;Gorospe M;Gudkov AV;Hall MN;Hekimi S;Helfand SL;Karlseder J;Kenyon C;Kroemer G;Longo V;Nussenzweig A;Osiewacz HD;Peeper DS;Rando TA;Rudolph KL;Sassone-Corsi P;Serrano M;Sharpless NE;Skulachev VP;Tilly JL;Tower J;Verdin E;Vijg J
通讯作者：
Vijg J