학술논문
NTCP deficiency in mice protects against obesity and hepatosteatosis.
Document Type
Academic Journal
Author
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.; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, 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.; Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
Source
Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
Subject
Language
English
Abstract
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.