Back to Search
Start Over
A New Treatment for Chronic Hepatitis B and D Offers Novel Insights Into Obesity and Hepatic Steatosis
- Source :
- Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 3, Pp 649-651 (2020), Cellular and Molecular Gastroenterology and Hepatology
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Bile acids are important metabolic signaling molecules. Bile acid receptor activation promotes body weight loss and improves glycemic control. The incretin hormone GLP-1 and thyroid hormone activation of T4 to T3 have been suggested as important contributors. Here, we identify the hepatic bile acid uptake transporter NaOrganic anion transporting polypeptide (OATP)1a/1b KO mice with or without reconstitution with human OATP1B1 in the liver were treated with the NTCP inhibitor Myrcludex B for 3.5 weeks after the onset of obesity induced by high fat diet-feeding. Furthermore, radiolabeled T4 was injected to determine the role of NTCP and OATPs in thyroid hormone clearance from plasma.Inhibition of NTCP by Myrcludex B in obese Oatp1a/1b KO mice inhibited hepatic clearance of bile acids from portal and systemic blood, stimulated GLP-1 secretion, reduced body weight, and decreased (hepatic) adiposity. NTCP inhibition did not affect hepatic T4 uptake nor lead to increased thyroid hormone activation. Myrcludex B treatment increased fecal energy output, explaining body weight reductions amongst unaltered food intake and energy expenditure.Pharmacologically targeting hepatic bile acid uptake to increase bile acid signaling is a novel approach to treat obesity and induce GLP1- secretion.
- Subjects :
- Male
medicine.medical_specialty
Organic Cation Transport Proteins
Organic Anion Transporters, Sodium-Dependent
Mice, Transgenic
Diet, High-Fat
Gastroenterology
Bile Acids and Salts
Lipopeptides
Mice
Chronic hepatitis
Glucagon-Like Peptide 1
Internal medicine
medicine
Animals
Humans
Obesity
lcsh:RC799-869
Hepatology
Symporters
business.industry
Liver-Specific Organic Anion Transporter 1
medicine.disease
Disease Models, Animal
Editorial
Liver
Female
lcsh:Diseases of the digestive system. Gastroenterology
Steatosis
business
Subjects
Details
- Language :
- English
- Volume :
- 10
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....52358f1cf6e2f8ac997744bcd142b60b