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高脂饮食肥胖抵抗小鼠表现出独特表型,与增强的脂代谢相关联。

Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism.

机构信息

Plants for Human Health Institute, NC State University, 600 Laureate Way, Kannapolis, NC 28081, USA.

Department of Food, Bioprocessing, and Nutrition Sciences, NC State University, 400 Dan Allen Drive, Raleigh, NC 27695, USA.

出版信息

Nutrients. 2024 Jan 4;16(1):171. doi: 10.3390/nu16010171.

DOI:10.3390/nu16010171
PMID:38202000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10780630/
Abstract

Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of . Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.

摘要

个体代谢的差异可能会显著影响肥胖易感性,表现为对现代高热量饮食的肥胖易感(超级应答者)和肥胖抵抗(非应答者)表型。在这项研究中,将 C57BL/6J 小鼠(n = 76)随机分为低脂饮食(LFD)或高脂饮食(HFD)组,分别喂养 6 周,然后选择正常肥胖(HFD)、非应答者(NR)、超级应答者(SR)或超级应答者切换回低脂饮食(SR-LFD)继续喂养 8 周。尽管 SR 组的呼吸交换率(RER)与 NR 组相似,但 SR 组的体重、瘦体重和脂肪体重、总水量和游离水量增加幅度最大,这在一定程度上归因于饲料效率的提高。切换至 LFD 足以使 SR-LFD 组的大多数观察到的生理变化恢复正常;然而,自发体力活动和运动能力并未恢复到基础水平。NR 组的食物摄入量最高,饲料效率最低,光照(休息)周期的耗氧量增加,暗(活跃)周期的体力活动增加,两个周期的产热量增加。这些变化是在食物摄入量和粪便参数没有变化的情况下观察到的;然而,NR 粪便中的脂质含量较低,NR 粪便微生物组的特征是丰度降低。总之,我们的研究结果表明,NR 组在骨骼肌中代谢过多膳食脂肪的能力增强,而运动能力降低,这种情况在整个研究期间持续存在。这些发现强调了需要进一步全面研究肥胖抵抗的机制,因为这对人类减肥策略具有潜在的意义。

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