The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation

Authors

Sung Ho Lee
Jong Min Choi
Sung Yun Jung
Aaron R Cox
Sean M Hartig
David D Moore
Kang Ho Kim

Publication Date

1-1-2021

Journal

Biochemical and Biophysical Research Communications

DOI

10.1016/j.bbrc.2020.10.086

PMID

33168190

PMCID

PMC7785631

PubMedCentral® Posted Date

1-1-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

3T3-L1 Cells, Adipogenesis, Animals, Bile Acids and Salts, Cattle, Fibroblasts, Lipogenesis, Liver, Male, Mice, Mice, Inbred C57BL, Obesity, Orosomucoid, Protein Isoforms, Proteomics/, bile acid, hepatokine, orosomucoid, adipogenesis, lipogenesis, obesity

Abstract

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells and mouse stromal vascular fibroblasts. ORM suppressed adipocyte differentiation and strongly inhibited gene expression of adipogenic transcription factors such as C/EBPβ, KLF5, C/EBPα, and PPARγ. Taken together, our data clearly suggest that bile acid-induced ORM secretion from the liver blocks adipocyte differentiation, potentially linked to anti-obesity effect of bile acids.

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