Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", UFR Santé, 22 Boulevard Gambetta, 76000, Rouen, France.
Institute for Research and Innovation in Biomedicine (IRIB), Univ Rouen Normandie, 76000, Rouen, France.
Sci Rep. 2024 Aug 27;14(1):19835. doi: 10.1038/s41598-024-70931-4.
Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.
肥胖通常与性别依赖的代谢并发症有关，其中改变的肠道屏障功能和肠道微生物群起作用。我们旨在描述高脂肪饮食对这些参数的性别依赖性影响。雄性和雌性 C57BL/6 小鼠在 14 周（W14）期间接受标准（SD）或高脂肪饮食（HFD；60％的热量来自脂肪）。评估了身体成分、葡萄糖耐量、胰岛素敏感性、肠道通透性、结肠表达参与炎症反应和肠道屏障功能的 44 个基因、盲肠微生物群、血浆脂肪因子和白色脂肪组织反应。与 SD 小鼠相比，雄性和雌性 HFD 小鼠的体重和脂肪量增加以及葡萄糖耐量降低。然而，只有雄性 HFD 小鼠倾向于发展与周围脂肪组织中 Tnfα 和 Ccl2 mRNA 表达增加相关的胰岛素抵抗。相比之下，只有雌性 HFD 小鼠显示出明显的肠道高通透性，这与结肠炎症反应的改变更为明显相关。在两性中，盲肠微生物群丰富度明显降低（观察到的物种），并且在门或科水平上具有性别依赖性的修饰，例如雌性中 Bacillota 和 Lachnospiraceae 的相对丰度降低，雄性中 Bacteroidaceae 的相对丰度增加。有趣的是，这些微生物群改变中的一些与外周代谢和炎症标志物相关。总之，雄性和雌性小鼠对高脂肪饮食有不同的反应，表现为肠道微生物群、肠道屏障功能、结肠和白色脂肪组织炎症、代谢标志物和体重增加的特异性改变。应该在进一步的研究中阐明潜在的机制。
