NTCP deficiency in mice protects against obesity and hepatosteatosis
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 cotransporting 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 and G protein-coupled bile acid receptor-double KO (TGR5-double KO) mice were equally protected against diet-induced obesity as NTCP-single KO mice. NTCP-KO mice displayed decreased intestinal fat absorption and a trend toward 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.
127197.2-20190701161947-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf
Publisher's version
openaccess
CC BY
3.67 MB
Adobe PDF
63d35098a67a030fee4b6173164f8046