The metabolic advantage of being young and male in obesity treatment outcomes in mice.

npj Metabolic Health and Disease Pub Date : 2025-08-01 DOI:10.1038/s44324-025-00065-2

Amanda S Dirnberger, Elen Yanina Aguirre-Rodriguez, Elias Carlos Aguirre-Rodriguez, John O Degraft Hanson, Yanping Sun, Dave Delima, Benjamin F Bykov, Aneirson Francisco da Silva, Marko Kraljević, Fernando Augusto Silva Marins, Ana Bf Emiliano

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Abstract

Although diversity in clinical trials is important to test the efficacy of a treatment, weight loss trials rarely account for age and sex. To highlight this deficiency, we set out to test whether age and sex affect WAT mobilization after weight loss surgery or intermittent fasting, in an obese mouse model. Here we show that male sex, youth, and WAT transcriptomic plasticity are characteristics associated with improved weight loss outcomes. Conversely, aging impairs WAT mobilization and transcriptomic plasticity. Greater surgical weight loss is associated with changes in the expression of genes relevant to the IL17 inflammatory signaling pathway, angiotensin converting enzyme 2 (ACE2) signaling, lipolysis, carbohydrate metabolism and adipocyte differentiation. In conclusion, female sex and older age appear to hinder molecular processes necessary for the reversal of WAT expansion. Future studies should examine the relevance of these findings to human obesity therapeutics.

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年轻和雄性在小鼠肥胖治疗结果中的代谢优势。

尽管临床试验的多样性对测试治疗效果很重要，但减肥试验很少考虑到年龄和性别。为了突出这一缺陷，我们开始在肥胖小鼠模型中测试年龄和性别是否会影响减肥手术或间歇性禁食后WAT的动员。本研究表明，男性、年轻和WAT转录组可塑性是改善减肥结果的相关特征。相反，衰老损害WAT的动员和转录组可塑性。手术后体重减轻与il - 17炎症信号通路、血管紧张素转换酶2 （ACE2）信号通路、脂肪分解、碳水化合物代谢和脂肪细胞分化相关基因的表达变化有关。综上所述，女性和老年似乎阻碍了逆转WAT扩张所必需的分子过程。未来的研究应该检验这些发现与人类肥胖治疗的相关性。

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npj Metabolic Health and Disease

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