Early-life gut microbiota protects against obesity in later life by regulating adipocytes thermogenesis
10.3760/cma.j.cn311282-20240701-00293
- VernacularTitle:生命早期肠道菌群的建立通过编程脂肪细胞产热能力降低远期肥胖发生
- Author:
Jiali FANG
1
;
Xue LONG
;
Hong ZHONG
;
Xianwei CUI
Author Information
1. 南京医科大学附属妇产医院（南京市妇幼保健院）医学研究中心 210004
- Keywords:
Early-life;
Gut microbiota;
Adipose tissue;
Thermogenesis;
Obesity
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(10):872-878
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore whether disrupted colonization of the gut microbiota in early life accelerates the development of obesity later in life through programming adipose thermogenesis.Methods:Neonatal mice were treated with a mixture of antibiotics (ABX), and 16S rRNA sequencing confirmed that ABX treatment disrupted the establishment of gut microbiota. The mice were monitored for changes in body weight and fat content at weaning, adulthood, and under a high-fat diet (HFD) to assess obesity phenotypes. Additionally, glucose tolerance and insulin tolerance tests were conducted, along with measurements of blood glucose and lipid levels, to evaluate changes in glucose and lipid metabolism. The expression of uncoupling protein 1 (UCP1) in adipose tissue was assessed through immunohistochemistry and Western blotting to evaluate alterations in adipocyte thermogenic capacity.Results:The analysis of 16S rRNA sequencing technology revealed that ABX treatment significantly reduced both α- and β-diversity of the gut microbiota. Compared to untreated mice, the microbial composition in ABX treated mice showed significant differences, with a notable reduction in the abundance of beneficial bacteria, including Lachnospiraceae_NK4A136_group and Akkermansia muciniphila ( A. muciniphia). Subsequent monitoring indicated that ABX treatment did not affect body weight or fat content during the lactation period. However, a significant decrease in surface temperature was observed in the ABX group, specifically in the interscapular region. Immunohistochemistry and Western blot of UCP1 demonstrated impaired thermogenic capacity in adipose tissue. Interestingly, the impaired thermogenesis persisted in adult mice, leading to a decreased cold tolerance, although no changes of metabolic dysfunction, including body weight, body fat percentage, serum insulin and triglyceride levels, glucose tolerance, and insulin sensitivity. Upon switching to HFD, ABX-exposed mice exhibited significant increases in body weight, fat mass, and serum glucose, indicating a greater susceptibility to obesity. Further thermographic analysis and UCP1 detection suggested that this susceptibility to obesity was also linked to impaired thermogenic capacity in adipose tissue. Conclusion:Early-life gut microbiota is a critical determinant of long-term adipose thermogenesis. Disruption of the microbiota enhances the effect of diet-induced obesity.
