Bachmann Alexis Maximilien, Morel Jean-David, El Alam Gaby, Rodríguez-López Sandra, Imamura de Lima Tanes, Goeminne Ludger J E, Benegiamo Giorgia, Loric Sylvain, Conti Marc, Sleiman Maroun Bou, Auwerx Johan
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Inserm U938 CRSA, St Antoine University Hospital, Paris, France.
iScience. 2022 May 25;25(6):104468. doi: 10.1016/j.isci.2022.104468. eCollection 2022 Jun 17.
The sharp increase in obesity prevalence worldwide is mainly attributable to changes in physical activity and eating behavior but the metabolic and clinical impacts of these obesogenic conditions vary between sexes and genetic backgrounds. This warrants personalized treatments of obesity and its complications, which require a thorough understanding of the diversity of metabolic responses to high-fat diet intake. By analyzing nine genetically diverse mouse strains, we show that much like humans, mice exhibit a huge variety of physiological and biochemical responses to high-fat diet. The strains exhibit various degrees of alterations in their phenotypic makeup. At the transcriptome level, we observe dysregulations of immunity, translation machinery, and mitochondrial genes. At the biochemical level, the enzymatic activity of mitochondrial complexes is affected. The diversity across mouse strains, diets, and sexes parallels that found in humans and supports the use of diverse mouse populations in future mechanistic or preclinical studies on metabolic dysfunctions.
全球肥胖患病率的急剧上升主要归因于身体活动和饮食行为的变化，但这些致肥胖状况的代谢和临床影响在性别和遗传背景之间存在差异。这就需要对肥胖及其并发症进行个性化治疗，而这需要深入了解对高脂饮食摄入的代谢反应的多样性。通过分析九种基因不同的小鼠品系，我们发现，与人类一样，小鼠对高脂饮食表现出各种各样的生理和生化反应。这些品系在表型构成上表现出不同程度的改变。在转录组水平上，我们观察到免疫、翻译机制和线粒体基因的失调。在生化水平上，线粒体复合物的酶活性受到影响。小鼠品系、饮食和性别之间的多样性与人类相似，这支持在未来关于代谢功能障碍的机制或临床前研究中使用多样化的小鼠群体。
