FGF21 acts as a negative regulator of bile acid synthesisстатья из журнала
Аннотация: Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid homeostasis in vivo; its most closely related subfamily member, FGF19, is known to be a critical negative regulator of bile acid synthesis. To delineate whether FGF21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native FGF21 and long-acting FGF21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary hepatocytes and in rodent and monkey models. FGF21 acutely induced ERK phosphorylation and inhibited Cyp7A1 mRNA expression in primary hepatocytes and in different rodent models, although less potently than recombinant human FGF19. Long-term administration of FGF21 in mice fed a standard chow diet resulted in a 50-60% decrease in bile acid levels in the liver and small intestines and consequently a 60% reduction of bile acid pool size. In parallel, colonic and fecal bile acid was decreased, whereas fecal cholesterol and fatty acid excretions were elevated. The long-acting FGF21 analog showed superiority to recombinant human FGF21 and FGF19 in decreasing bile acid levels with long duration of effect action in mice. Long-term administration of the long-acting FGF21 analogs in obese cynomolgus monkeys suppressed plasma total bile acid and 7α-hydroxy-4-cholesten-3-one levels, a biomarker for bile acid synthesis. Collectively, these data reveal a previously unidentified role of FGF21 in bile acid metabolism as a negative regulator of bile acid synthesis.
Год издания: 2018
Издательство: Bioscientifica
Источник: Journal of Endocrinology
Ключевые слова: Fibroblast Growth Factor Research, Epigenetics and DNA Methylation, Kruppel-like factors research
Другие ссылки: Journal of Endocrinology (PDF)
Journal of Endocrinology (HTML)
PubMed (HTML)
Journal of Endocrinology (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 237
Выпуск: 2
Страницы: 139–152