Telmisartan attenuates the inflamed mesenteric adipose tissue in spontaneous colitis by mechanisms involving regulation of neurotensin/microRNA-155 pathway.

Abstract

Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10(-)/(-) mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease.

• Authors: Yi Li, Lugen Zuo, Weiming Zhu, Jianfeng Gong, Wei Zhang, Zhen Guo, Lili Gu, Ning Li, Jieshou Li
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 93 Issue 4 Pg. 461-9 (Feb 15 2015) ISSN: 1873-2968 [Electronic] England
• PMID: 25576685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Benzoates
• MicroRNAs
• Mirn155 microRNA, mouse
• Neurotensin
• Telmisartan

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology, therapeutic use)
• Animals
• Benzimidazoles (pharmacology, therapeutic use)
• Benzoates (pharmacology, therapeutic use)
• Colitis (drug therapy, metabolism, pathology)
• Inflammation (drug therapy, metabolism, pathology)
• Intra-Abdominal Fat (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C3H
• Mice, Knockout
• MicroRNAs (antagonists & inhibitors, physiology)
• Neurotensin (antagonists & inhibitors, physiology)
• Telmisartan