Bile acid receptor TGR5 is critically involved in preference for dietary lipids and obesity

J Nutr Biochem. 2020 Feb:76:108298. doi: 10.1016/j.jnutbio.2019.108298. Epub 2019 Nov 23.

Abstract

We investigated the implication of Takeda G protein-coupled receptor 5 (TGR5) in fat preference and fat sensing in taste bud cells (TBC) in C57BL/6 wild-type (WT) and TGR5 knock out (TGR5-/-) male mice maintained for 20 weeks on a high-fat diet (HFD). We also assessed the implication of TGR5 single nucleotide polymorphism (SNP) in young obese humans. The high-fat diet (HFD)-fed TGR5-/- mice were more obese, marked with higher liver weight, lipidemia and steatosis than WT obese mice. The TGR5-/- obese mice exhibited high daily food/energy intake, fat mass and inflammatory status. WT obese mice lost the preference for dietary fat, but the TGR5-/- obese mice exhibited no loss towards the attraction for lipids. In lingual TBC, the fatty acid-triggered Ca2+ signaling was decreased in WT obese mice; however, it was increased in TBC from TGR5-/- obese mice. Fatty acid-induced in vitro release of GLP-1 was higher, but PYY concentrations were lower, in TBC from TGR5-/- obese mice than those in WT obese mice. We noticed an association between obesity and variations in TGR5 rs11554825 SNP. Finally, we can state that TGR5 modulates fat eating behavior and obesity.

Keywords: Fat; Fatty acid; Lipids; Obesity; Taste bud.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism*
  • Blood Glucose / metabolism
  • Calcium / metabolism
  • Diet, High-Fat
  • Dietary Fats
  • Disease Models, Animal
  • Fatty Liver
  • Food Preferences*
  • Inflammation
  • Insulin / metabolism
  • Lipids / chemistry*
  • Lipopolysaccharides / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Obesity / genetics
  • Obesity / metabolism*
  • Polymorphism, Single Nucleotide
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism*

Substances

  • Bile Acids and Salts
  • Blood Glucose
  • Dietary Fats
  • Gpbar1 protein, mouse
  • Insulin
  • Lipids
  • Lipopolysaccharides
  • Receptors, G-Protein-Coupled
  • Calcium