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  

Early-life gut microbiota protects against obesity in later life by regulating adipocytes thermogenesis

作　　者：方家丽 龙雪 仲红 崔县伟[1] Fang Jiali;Long Xue;Zhong Hong;Cui Xianwei(Nanjing Women and Children′s Healthcare Institute,Women′s Hospital of Nanjing Medical University(Nanjing Women and Children′s Healthcare Hospital),Nanjing 210004,China;School of Food Science and Pharmaceutical Engineering,Nanjing Normal University,Nanjing 210023,China)

机构地区：[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 [2]南京师范大学食品与制药工程学院,210023

出　　处：《中华内分泌代谢杂志》2024年第10期872-878,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(82070879,82470890)。

摘　　要：目的探究生命早期肠道菌群的建立是否可以通过编程脂肪细胞产热能力影响远期肥胖发生的易感性。方法采用抗生素混合物(ABX)处理新生小鼠,经16S rRNA测序证实ABX处理引发生命早期肠道菌群建立紊乱。继续追踪上述小鼠在断奶时、成年后以及高脂饮食状态下的体重、体脂含量,评估小鼠肥胖表型变化;通过分析小鼠血糖、血脂水平,开展葡萄糖耐量和胰岛素耐量试验,评估小鼠糖脂代谢能力变化;通过免疫组化、Western印迹法检测脂肪组织解偶联蛋白1(UCP1)的表达,评估小鼠脂肪细胞产热能力变化。结果16S rRNA测序显示ABX处理显著降低了新生小鼠肠道菌群的α多样性和β多样性,与未处理小鼠相比,ABX组小鼠菌群构成上差异显著,益生菌如毛螺菌(Lachnospiraceae_NK4A136_group)属NK4A136群、嗜黏蛋白阿克曼菌(Akkermansia muciniphila,AKK)等丰度显著降低。追踪监测发现,ABX处理并未影响小鼠哺乳期的体重以及体脂含量,小鼠体表温度尤其肩胛区显著降低,UCP1免疫组化和Western印迹结果显示脂肪组织产热能力受损。这种对脂肪组织产热能力的影响可以持续到成年,导致小鼠寒冷抵抗能力降低,但上述改变并未引发正常饮食下小鼠体重、体脂、血糖以及葡萄糖耐受性和胰岛素敏感性的改变。当更换高脂饮食后,ABX处理小鼠体重、体脂含量显著增长,血糖水平升高明显,提示小鼠更容易发生肥胖,进一步热成像、UCP1含量检测揭示这种肥胖易感性同样与脂肪组织产热能力受损有关。结论生命早期肠道菌群的建立是调控脂肪细胞产热能力的关键,扰乱健康菌群建立容易引发成年后高脂饮食诱导的肥胖。ObjectiveTo explore whether disrupted colonization of the gut microbiota in early life accelerates the development of obesity later in life through programming adipose thermogenesis.MethodsNeonatal 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.ResultsThe analysis of 16S rRNA sequencing technology revealed that ABX treatment significantly reduced bothα-andβ-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.F

关 键 词：生命早期 肠道菌群 脂肪组织 产热活性 肥胖 

分 类 号：R589.2[医药卫生—内分泌]