法尼甾体X受体
代谢组
胆汁酸
代谢组学
代谢途径
生物
空腹血糖受损
糖耐量受损
核受体
新陈代谢
内科学
内分泌学
生物化学
医学
生物信息学
糖尿病
2型糖尿病
转录因子
基因
作者
Yun-Chung Hsiao,Yifei Yang,Chih‐Wei Liu,Jingya Peng,Jiahao Feng,Haoduo Zhao,Taylor Teitelbaum,Kun Lü
标识
DOI:10.1021/acs.jproteome.3c00475
摘要
The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in Fxr-null (Fxr–/–) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. Fxr–/– mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid β-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.
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