Evidence of functional bile acid signaling pathways in adipocytes

Mol Cell Endocrinol. 2019 Mar 1:483:1-10. doi: 10.1016/j.mce.2018.12.006. Epub 2018 Dec 11.

Abstract

Background and aim: Bile acids (BA) are increasingly recognized as pleiotropic and hormone-like signaling molecules with metabolic and endocrine functions. However, the role of BA in white adipocyte physiology remains somewhat obscure. It was the aim to investigate the BA receptors (FXR, TGR5) and FGFR1 (Fibroblast growth factor receptor 1) as well as Bsep (bile salt export pump) in white adipocytes and in murine and human adipose tissue (AT) and to investigate effects of different BA species in adipocyte physiology.

Patients, material and methods: Receptor mRNA expression was quantified by real-time PCR in mice, humans and during 3T3-L1 pre-adipocyte differentiation. Adipokines were measured by ELISA upon stimulation by several BA. Effects of BA on TNF- and LPS-induced MCP-1 secretion and lipolysis were analyzed. TNF-induced lipolysis was investigated by glycerol assay.

Results: The present data provide for the first time a detailed expression profile of FXR, TGR5, FGFR1, and Bsep during adipocyte differentiation and in murine and human AT. FGFR1 expression is upregulated in adipose tissue of LPS-injected animals. Several BA regulate secretion of adipokines such as adiponectin and resistin differentially. Importantly, TNF- and LPS-induced MCP-1 release from adipocytes as well as TNF-induced lipolysis can be antagonized by cholic acid (CA) and deoxycholic acid (DCA).

Conclusions: The present data provide evidence of functional BA signaling pathways in adipocytes and argue for certain MCP-1 related anti-inflammatory effects of BA in TNF- and LPS-induced inflammation, whereas pro-inflammatory resistin is induced by CA and glycocholic acid (GCA). Systemic bile acids might represent a hormonal network regulating white adipocyte physiology including lipolysis.

Keywords: Adipocytes; Adipokines; Adipose tissue; Bile acid receptor; Bile acids.

MeSH terms

  • 3T3-L1 Cells
  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 11 / metabolism
  • Adipocytes, White / cytology*
  • Adipocytes, White / drug effects
  • Adipocytes, White / metabolism
  • Adipokines / metabolism
  • Adult
  • Animals
  • Bile Acids and Salts / metabolism*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipolysis / drug effects
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 11
  • Adipokines
  • Bile Acids and Salts
  • Lipopolysaccharides
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor
  • Receptor, Fibroblast Growth Factor, Type 1