Delayed Gut Colonization Changes Future Insulin Resistance and Hepatic Gene Expression but Not Adiposity in Obese Mice.

IF 3.8 Q2 ENDOCRINOLOGY & METABOLISM
Journal of Obesity Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI:10.1155/2024/5846674
Maria B B Ebert, Caroline M J Mentzel, Anders Brunse, Lukasz Krych, Camilla H F Hansen
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引用次数: 0

Abstract

Objective: The importance of early microbial dysbiosis in later development of obesity and metabolic disorders has been a subject of debate. Here we tested cause and effect in mice.

Methods: Germ-free male Swiss Webster mice were colonized in a specific-pathogen-free (SPF) facility at 1 week (1W) and 3 weeks (3W) of age. They were challenged with a high-fat diet and their responses were compared with SPF mice. Gut microbiota was analyzed by 16S rRNA gene sequencing. Moreover, RNA sequencing of the liver was performed on additional 3W and SPF mice on a regular chow diet.

Results: There were no significant differences in weight, food consumption, epididymal fat weight, HbA1c levels, and serum insulin and leptin, whereas the early germ-free period resulted in mice with impaired glucose tolerance. Both the 1W and 3W group peaked 56% (p < 0.05) and 66% (p < 0.01) higher in blood glucose than the SPF control group, respectively. This was accompanied by a 45% reduction in the level of the anti-inflammatory cytokine IL-10 in the 1W mice (p < 0.05). There were no differences in the gut microbiota between the groups, indicating that all mice colonized fully after the germ-free period. Marked effects on hepatic gene expression (728 differentially expressed genes with adjusted p < 0.05 and a fold change ± 1.5) suggested a potential predisposition to a higher risk of developing insulin resistance in the 3W group.

Conclusions: Lack of microbes early in life had no impact on adiposity but led to insulin resistance and altered liver gene expression related to glucose metabolism in mice. The study strongly supports the notion that microbial signaling to the liver in the beginning of life can alter the host's risk of developing metabolic disorder later in life.

延迟肠道定植会改变肥胖小鼠未来的胰岛素抵抗和肝脏基因表达,但不会改变脂肪含量。
目的:早期微生物菌群失调对日后肥胖症和代谢紊乱的重要影响一直是一个争论的话题。在此,我们对小鼠的因果关系进行了测试:无菌雄性瑞士韦伯斯特小鼠在1周龄(1W)和3周龄(3W)时在无特定病原体(SPF)设施中定植。它们接受高脂肪饮食挑战,并将其反应与 SPF 小鼠进行比较。通过 16S rRNA 基因测序分析了肠道微生物群。此外,还对其他 3W 小鼠和以普通饲料为食的 SPF 小鼠的肝脏进行了 RNA 测序:结果:小鼠的体重、食量、附睾脂肪重量、HbA1c水平、血清胰岛素和瘦素没有明显差异,而早期无菌期导致小鼠糖耐量受损。与 SPF 对照组相比,1W 和 3W 组的血糖峰值分别高出 56% (p < 0.05) 和 66% (p < 0.01)。与此同时,1W 组小鼠的抗炎细胞因子 IL-10 水平降低了 45%(p < 0.05)。各组之间的肠道微生物群没有差异,这表明所有小鼠在无菌期后都完全定植。对肝脏基因表达的明显影响(728个差异表达基因,调整后的p < 0.05,折合变化± 1.5)表明,3W组小鼠可能有更高的胰岛素抵抗风险:结论:小鼠在生命早期缺乏微生物不会对脂肪产生影响,但会导致胰岛素抵抗和与葡萄糖代谢相关的肝脏基因表达改变。这项研究有力地支持了这样一种观点,即生命初期向肝脏发出的微生物信号可改变宿主日后患上代谢紊乱的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Obesity
Journal of Obesity ENDOCRINOLOGY & METABOLISM-
CiteScore
7.50
自引率
3.00%
发文量
19
审稿时长
21 weeks
期刊介绍: Journal of Obesity is a peer-reviewed, Open Access journal that provides a multidisciplinary forum for basic and clinical research as well as applied studies in the areas of adipocyte biology & physiology, lipid metabolism, metabolic syndrome, diabetes, paediatric obesity, genetics, behavioural epidemiology, nutrition & eating disorders, exercise & human physiology, weight control and health risks associated with obesity.
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