ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2025
Inhibition of SREBP-1c rescues hepatic CYP7B1 expression and bile acid synthesis in malnourished mice.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of oxysterol 7α-hydroxylase (CYP7B1), a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by sterol regulatory element-binding protein-1c (SREBP-1c), a master regulator of lipid metabolism. Mice were maintained on a low-protein, low-fat, or isocaloric control chow until 8 wk of age, when livers were harvested for proteome profiling, western blot, reverse transcription quantitative real-time PCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c inhibitors fatostatin and betulin to determine whether this therapeutic strategy rescues CYP7B1 expression and bile acid synthesis in malnutrition. Malnutrition decreased the bile acid pool size and altered the expression of multiple hepatic cytochrome P450 enzymes, with profound depletion of CYP7B1, in males but not females. Malnutrition activated SREBP-1c and led to its enrichment at a
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