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NTCP deficiency in mice protects against obesity and hepatosteatosis.
Journal article

NTCP deficiency in mice protects against obesity and hepatosteatosis.

  • Donkers JM Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Kooijman S Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, Netherlands.
  • Slijepcevic D Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Kunst RF Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Roscam Abbing RL Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Haazen L Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • de Waart DR Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Levels JH Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • Schoonjans K Laboratory of Metabolic Signaling, École Polytechnique Fédérale de Lausanne,, Lausanne, Switzerland.
  • Rensen PC Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, Netherlands.
  • Oude Elferink RP Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
  • van de Graaf SF Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
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  • 2019-06-26
Published in:
  • JCI insight. - 2019
Hepatology
Metabolism
Obesity
Transport
Adipose Tissue, Brown
Animals
Bile Acids and Salts
Blood Glucose
Body Weight
Cholesterol
Diet, High-Fat
Dietary Fats
Energy Metabolism
Fatty Liver
Glucose Tolerance Test
Insulin
Intestinal Absorption
Mice
Mice, Knockout
Obesity
Organic Anion Transporters, Sodium-Dependent
Receptors, G-Protein-Coupled
Symporters
Triglycerides
Weight Gain
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/22214
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