| First Author | Donkers JM | Year | 2019 |
| Journal | JCI Insight | Volume | 5 |
| PubMed ID | 31237863 | Mgi Jnum | J:295423 |
| Mgi Id | MGI:6460500 | Doi | 10.1172/jci.insight.127197 |
| Citation | Donkers JM, et al. (2019) NTCP deficiency in mice protects against obesity and hepatosteatosis. JCI Insight 5 |
| abstractText | 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. |
