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温和的环境冷应激可提高肥胖雌性小鼠的肌肉钙循环和运动适应能力。

Mild Cold Stress at Ambient Temperature Elevates Muscle Calcium Cycling and Exercise Adaptations in Obese Female Mice.

机构信息

Molecular Metabolism in Cancer and Ageing, Department of Biomedical Sciences, Faculty of Health, University of Copenhagen, Copenhagen 2200, Denmark.

Muscle Plasticity in Health and Disease, Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, L2A 3A1, Canada.

出版信息

Endocrinology. 2024 Aug 27;165(10). doi: 10.1210/endocr/bqae102.

DOI:10.1210/endocr/bqae102
PMID:39136248
Abstract

CONTEXT

Housing temperature is a critical regulator of mouse metabolism and thermoneutral housing can improve model translation to humans. However, the impact of housing temperature on the ability of wheel running exercise training to rescue the detrimental effect of diet-induced obese mice is currently not fully understood.

OBJECTIVE

To investigate how housing temperature affects muscle metabolism in obese mice with regard to calcium handling and exercise training (ET) adaptations in skeletal muscle, and benefits of ET on adiposity and glucometabolic parameters.

METHODS

Lean or obese female mice were housed at standard ambient temperature (22 °C) or thermoneutrality (30 °C) with/without access to running wheels. The metabolic phenotype was investigated using glucose tolerance tests, indirect calorimetry, and body composition. Molecular muscle adaptations were measured using immunoblotting, qPCR, and spectrophotometric/fluorescent assays.

RESULTS

Obese female mice housed at 22 °C showed lower adiposity, lower circulating insulin levels, improved glucose tolerance, and elevated basal metabolic rate compared to 30 °C housing. Mice exposed to voluntary wheel running exhibited a larger fat loss and higher metabolic rate at 22 °C housing compared to thermoneutrality. In obese female mice, glucose tolerance improved after ET independent of housing temperature. Independent of diet and training, 22 °C housing increased skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) activity. Additionally, housing at 22 °C elevated the induction of training-responsive muscle proteins in obese mice.

CONCLUSION

Our findings highlight that housing temperature significantly influences adiposity, insulin sensitivity, muscle physiology, and exercise adaptations in diet-induced obese female mice.

摘要

背景

居住温度是调节小鼠代谢的关键因素,适宜温度的居住环境可以提高模型向人类的转化效果。然而,居住温度对通过转轮运动训练来改善肥胖小鼠的不利影响的能力的影响目前还不完全清楚。

目的

研究居住温度如何影响肥胖小鼠的肌肉代谢,包括钙处理以及骨骼肌运动训练(ET)适应性,以及 ET 对肥胖和糖代谢参数的益处。

方法

将瘦鼠或肥胖雌性小鼠分别饲养在标准环境温度(22°C)或热中性温度(30°C)下,并允许或不允许使用转轮。使用葡萄糖耐量试验、间接测热法和身体成分分析来研究代谢表型。使用免疫印迹、qPCR 和分光光度法/荧光法测量肌肉的分子适应性。

结果

22°C 环境温度下饲养的肥胖雌性小鼠与 30°C 环境温度相比,体脂率更低,循环胰岛素水平更低,葡萄糖耐量更好,基础代谢率更高。与热中性温度相比,在 22°C 环境温度下进行自愿转轮运动的小鼠体脂损失更大,代谢率更高。在肥胖雌性小鼠中,无论居住温度如何,ET 均可改善葡萄糖耐量。独立于饮食和训练,22°C 环境温度增加了骨骼肌肌浆网 Ca2+-ATP 酶(SERCA)的活性。此外,22°C 环境温度增加了肥胖小鼠训练响应性肌肉蛋白的诱导。

结论

我们的研究结果表明,居住温度显著影响肥胖雌性小鼠的肥胖程度、胰岛素敏感性、肌肉生理学和运动适应性。

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