Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Li, H; Perino, A; Huang, Q; Von, Alvensleben, GVG; Banaei-Esfahani, A; Velazquez-Villegas, LA; Gariani, K; Korbelius, M; Bou, Sleiman, M; Imbach, J; Sun, Y; Li, X; Bachmann, A; Goeminne, LJE; Gallart-Ayala, H; Williams, EG; Ivanisevic, J; Auwerx, J; Schoonjans, K.
Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis.
Cell Metab. 2022; 34(10): 1594-1610.e4.
Doi: 10.1016/j.cmet.2022.08.015
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- Co-Autor*innen der Med Uni Graz
- Korbelius Melanie
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- Abstract:
- Bile acids (BAs) are complex and incompletely understood enterohepatic-derived hormones that control whole-body metabolism. Here, we profiled postprandial BAs in the liver, feces, and plasma of 360 chow- or high-fat-diet-fed BXD male mice and demonstrated that both genetics and diet strongly influence BA abundance, composition, and correlation with metabolic traits. Through an integrated systems approach, we mapped hundreds of quantitative trait loci that modulate BAs and identified both known and unknown regulators of BA homeostasis. In particular, we discovered carboxylesterase 1c (Ces1c) as a genetic determinant of plasma tauroursodeoxycholic acid (TUDCA), a BA species with established disease-preventing actions. The association between Ces1c and plasma TUDCA was validated using data from independent mouse cohorts and a Ces1c knockout mouse model. Collectively, our data are a unique resource to dissect the physiological importance of BAs as determinants of metabolic traits, as underscored by the identification of CES1C as a master regulator of plasma TUDCA levels.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Bile Acids and Salts - metabolism
- Carboxylic Ester Hydrolases - metabolism
- Diet, High-Fat - administration & dosage
- Homeostasis - administration & dosage
- Hormones - metabolism
- Liver - metabolism
- Male - administration & dosage
- Mice - administration & dosage
- Systems Analysis - administration & dosage
- Taurochenodeoxycholic Acid - administration & dosage