代谢功能障碍相关脂肪变性肝病伴晚期纤维化的血浆和粪便胆汁酸谱

IF 3.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Marion Pradeau, Sandrine Beaulieu, Véronique Paquet, Jocelyn Trottier, Mélanie Verreault, Stéphanie Ferland, Olivier Barbier, Anne-Marie Carreau
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引用次数: 0

摘要

胆汁酸(BAs)作为肝脏和肠道受体FXR的激素配体,刺激FGF-19和GLP-1的分泌。虽然MASLD与BA失调有关,但晚期纤维化对血浆和粪便BA谱的影响尚不清楚。我们比较了35个血浆和粪便BA浓度和定性池,包括原发性、继发性、非偶联性和偶联性BA,分别发生在晚期纤维化(F3-F4/4)个体(n=28)和非晚期纤维化个体(n=26)之间。中位年龄(IQR) (56 [48-65] vs 57[49-66]岁)、性别(62 vs 60%男性)和BMI (32 [29-36] vs 34[32-38] kg/m2)组间具有可比性。血浆总BA浓度在纤维化晚期升高(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma and fecal bile acids profiles in metabolic dysfunction-associated steatotic liver disease with advanced fibrosis.

Bile acids (BAs) act as hormonal ligands of hepatic and intestinal receptor FXR, stimulators of FGF-19 and GLP-1 secretion. While MASLD is linked to BA dysregulation, the effects of advanced fibrosis on plasma and fecal BA profiles remain unclear. We compared 35 plasmatic and fecal BA concentrations and qualitative pools, including primary, secondary, unconjugated and conjugated BAs in fasting state between individuals with advanced fibrosis stages (F3-F4/4) (n=28) and individuals without advanced fibrosis (n=26). Median age (IQR) (56 [48-65] vs 57 [49-66] yr), sex (62 vs 60% man) and BMI (32 [29-36] vs 34[32-38] kg/m2) were comparable between groups. Total plasmatic BA concentration was increased in the advanced stage of fibrosis (p<0.01), whereas total stool BA concentration did not differ between groups (p = 0.36). Participants with advanced fibrosis had higher CDCA family BAs, which was driven by increased glyco- and tauro-conjugated forms (p<0.05). Plasma unconjugated secondary BA LCA was also higher in advanced fibrosis (p<0.01), but we did not find change in intestinal microbiota BSH enzymatic activity, responsible for deconjugation of BA. There were no differences in FGF-19 and GLP-1 concentrations between groups. Overall, our results lead us to hypothesize that the increase in hepatic bile acid production in cases of MASLD with advanced fibrosis may occur mainly via the acid pathway, or leakage of BAs from the liver into the plasma caused by hepatic inflammation, without changes in intestinal BA metabolism. This profile of increased hydrophobic plasma BA may contribute to MASLD progression, inflammation and oxidative stress.

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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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