Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways.

Abstract

Telmisartan shows antihypertensive and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that telmisartan prevents adipogenesis in vitro and weight gain in vivo through activation of peroxisome proliferator-activated receptor (PPAR)-delta-dependent pathways in several tissues. In vitro, telmisartan significantly upregulated PPAR-delta expression in 3T3-L1 preadipocytes in a time- and dose-dependent manner. Other than enhancing PPAR-delta expression by 68.2+/-17.3% and PPAR-delta activity by 102.0+/-9.0%, telmisartan also upregulated PPAR-gamma expression, whereas neither candesartan nor losartan affected PPAR-delta expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-delta knockout mice. Administration of telmisartan did not influence food intake in mice. Telmisartan influenced several lipolytic and energy uncoupling related proteins (UCPs) and enhanced phosphorylated protein kinase A and hormone sensitive lipase but reduced perilipin expression and finally inhibited adipogenesis in 3T3-L1 preadipocytes. Telmisartan-associated reduction of adipogenesis in preadipocytes was significantly blocked after PPAR-delta gene knockout. Chronic telmisartan treatment upregulated the expressions of protein kinase A, hormone-sensitive lipase, and uncoupling protein 1 but reduced perilipin expression in adipose tissue and increased uncoupling protein 2 and 3 expression in skeletal muscle in wild-type mice but not in PPAR-delta knockout mice. We conclude that telmisartan prevents adipogenesis and weight gain through activation of PPAR-delta-dependent lipolytic pathways and energy uncoupling in several tissues.

• Authors: Hongbo He, Dachun Yang, Liqun Ma, Zhidan Luo, Shuangtao Ma, Xiaoli Feng, Tingbing Cao, Zhencheng Yan, Daoyan Liu, Martin Tepel, Zhiming Zhu
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 55 Issue 4 Pg. 869-79 (Apr 2010) ISSN: 1524-4563 [Electronic] United States
• PMID: 20176998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Benzoates
• Dietary Fats
• PPAR delta
• Uncoupling Agents
• Telmisartan

Topics

• Adipocytes (cytology, drug effects, metabolism)
• Adipose Tissue (drug effects, metabolism)
• Analysis of Variance
• Animals
• Benzimidazoles (metabolism, pharmacology)
• Benzoates (metabolism, pharmacology)
• Blotting, Western
• Cell Differentiation (drug effects)
• Cells, Cultured
• Dietary Fats (metabolism, pharmacology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Eating (drug effects)
• Fluorescent Antibody Technique
• Mice
• Mice, Knockout
• Obesity (metabolism, prevention & control)
• PPAR delta (genetics, metabolism)
• Signal Transduction (drug effects)
• Telmisartan
• Uncoupling Agents (metabolism)
• Weight Gain (drug effects)