Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet.

Abstract

TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids (BAs). TGR5 is thought to be a promising drug target for metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet (HFD). In the present study, we identified a naturally occurring limonoid, nomilin, as an activator of TGR5. Unlike BAs, nomilin did not exhibit the farnesoid X receptor ligand activity. Although the nomilin derivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a HFD for 9 weeks were further fed a HFD either alone or supplemented with 0.2%w/w nomilin for 77 days, nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance. Our results suggest a novel biological function of nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5.

• Authors: Eri Ono, Jun Inoue, Tsutomu Hashidume, Makoto Shimizu, Ryuichiro Sato
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 410 Issue 3 Pg. 677-81 (Jul 08 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21693102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Obesity Agents
• Benzoxepins
• Blood Glucose
• Dietary Fats
• Gpbar1 protein, mouse
• Hypolipidemic Agents
• Insulin
• Ligands
• Limonins
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Receptors, G-Protein-Coupled
• Trans-Activators
• Transcription Factors
• obacunone
• nomilin
• iodothyronine deiodinase type II
• Iodide Peroxidase

Topics

• Animals
• Anti-Obesity Agents (administration & dosage)
• Benzoxepins (administration & dosage, chemistry)
• Blood Glucose (drug effects)
• Citrus (chemistry)
• Diet (adverse effects)
• Dietary Fats (administration & dosage, adverse effects)
• Gene Expression (drug effects)
• HEK293 Cells
• Humans
• Hyperglycemia (drug therapy, etiology)
• Hypolipidemic Agents (administration & dosage)
• Insulin (blood)
• Iodide Peroxidase (genetics)
• Ligands
• Limonins (administration & dosage, chemistry)
• Male
• Mice
• Obesity (drug therapy, etiology)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Receptors, G-Protein-Coupled (agonists, antagonists & inhibitors)
• Trans-Activators (genetics)
• Transcription Factors