NTCP deficiency in mice protects against obesity and hepatosteatosis

JCI Insight. 2019 Jun 25;5(14):e127197. doi: 10.1172/jci.insight.127197.


Bile acids play a major role in the regulation of lipid and energy metabolism. Here we propose the hepatic bile acid uptake transporter Na+ taurocholate co-transporting polypeptide (NTCP) as a target to prolong postprandial bile acid elevations in plasma. Reducing hepatic clearance of bile acids from plasma by genetic deletion of NTCP moderately increased plasma bile acid levels, reduced diet-induced obesity, attenuated hepatic steatosis, and lowered plasma cholesterol levels. NTCP-G protein-coupled bile acid receptor (TGR5) double knockout mice were equally protected against diet-induced-obesity as NTCP single knockout mice. NTCP knockout mice displayed decreased intestinal fat absorption and a trend towards higher fecal energy output. Furthermore, NTCP deficiency was associated with an increased uncoupled respiration in brown adipose tissue, leading to increased energy expenditure. We conclude that targeting NTCP-mediated bile acid uptake can be a novel approach to treat obesity and obesity-related hepatosteatosis by simultaneously dampening intestinal fat absorption and increasing energy expenditure.

Keywords: Hepatology; Metabolism; Obesity; Transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Bile Acids and Salts / blood
  • Blood Glucose / metabolism
  • Body Weight
  • Cholesterol / blood
  • Diet, High-Fat*
  • Dietary Fats / metabolism
  • Energy Metabolism / genetics
  • Fatty Liver / genetics*
  • Fatty Liver / metabolism
  • Glucose Tolerance Test
  • Insulin / blood
  • Intestinal Absorption / genetics
  • Mice
  • Mice, Knockout
  • Obesity / genetics*
  • Obesity / metabolism
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Symporters / genetics*
  • Triglycerides / blood
  • Weight Gain / genetics*


  • Bile Acids and Salts
  • Blood Glucose
  • Dietary Fats
  • Gpbar1 protein, mouse
  • Insulin
  • Organic Anion Transporters, Sodium-Dependent
  • Receptors, G-Protein-Coupled
  • Symporters
  • Triglycerides
  • sodium-bile acid cotransporter
  • Cholesterol