Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 692, Issue 1-3, Pages 84-90Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.07.026
Keywords
Adipocyte; Adiponectin; AMP-activated protein kinase; Obesity; Peroxisome proliferator-activated receptor-gamma; Sirt1
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labor and Welfare (MHLW)
- Grants-in-Aid for Scientific Research [23591314, 24591338, 22390159, 24659392] Funding Source: KAKEN
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Telmisartan exerts anti-metabolic effects beyond its angiotensin receptor blockade activities, but the mechanisms have hitherto remained elusive. We sought to elucidate the peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-dependent and PPAR-gamma-independent mechanisms underlying the anti-metabolic effects of telmisartan in white adipose tissue. Nine-week-old male C57BL16 mice were fed with a 60% high-fat diet for 6 weeks, with 1 mg/kg telmisartan or vehicle administrated orally during the last 3 weeks. 3T3-L1 adipocytes were cultured with telmisartan either with 2-chloro-5-nitro-N-phenylbenzamide (GW9662), a selective irreversible antagonist of PPAR-gamma, or compound C, an ATP-competitive inhibitor of AMPK. Western blotting and semiquantitative RT-PCR analysis were used to assess adiponectin, Sirt1, and AMPK levels. Lipid accumulation was assessed by Oil red 0 staining. The activation of transcription factor PPAR-gamma 2 was evaluated by using a luciferase reporter assay for mPPAR-gamma 2 expression plasmid vector. Treatment with telmisartan increased serum adiponectin levels in high-fat diet-fed mice concomitantly with an upregulation of adiponectin mRNA in visceral adipose tissue. In vitro telmisartan treatment dose-dependently increased adiponectin mRNA in 3T3-L1 cells; the increase was inhibited by compound C, but not by GW9662. Telmisartan increased expression of Sirt1 mRNA and Sirt1 protein as well as the phosphorylation of AMPK in 3T3-L1 cells. Telmisartan can increase adiponectin production in white adipose tissue partly via a PPAR-gamma 2-independent mechanism. Precise understanding of this molecular mechanism will require further investigation. (C) 2012 Elsevier B.V All rights reserved.
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