Objectives: Telmisartan is an angiotensin II receptor blocker and selective modulator of peroxisome proliferator-activated receptor-γ reported to increase energy expenditure and improve glucose and lipid metabolism compared with other angiotensin II receptor blockers. As muscle fatty acid oxidation is a major determinant of energy expenditure, we investigated the effects of telmisartan on skeletal muscle fatty acid oxidation in a rat model of the metabolic syndrome.
Methods: We measured fatty acid oxidation in soleus muscles obtained from polydactylous (PD)/Cub rats fed a high sucrose, high fat diet and treated with either telmisartan or losartan. In addition, we measured fatty acid oxidation in soleus muscle tissue isolated from Sprague–Dawley rats, incubated for 3 h with either telmisartan or valsartan.
Results: Compared with treatment with losartan, treatment with telmisartan was associated with significantly greater palmitate oxidation in skeletal muscle (44.4 ± 2.9 versus 28.9 ± 3.2 nmol palmitate/g/2 h, P = 0.004) as well as significantly greater glucose tolerance and significantly lower body weight and visceral adiposity. In addition, in-vitro incubation of skeletal muscle with telmisartan induced significantly greater increase in palmitate oxidation than in-vitro incubation with valsartan (9.4 ± 1.6 versus 0.2 ± 4.3 nmol palmitate/g/h, P < 0.05). The increased fatty acid oxidation induced by telmisartan in vitro was blocked by addition of the peroxisome proliferator-activated receptor-γ antagonist GW9662 (−0.4 ± 1.8 nmol palmitate/g/h, P < 0.05).
Conclusion: The current results are consistent with the possibility that telmisartan may increase energy expenditure and protect against dietary induced obesity and features of the metabolic syndrome at least in part by increasing muscle fatty acid oxidation through activation of peroxisome proliferator-activated receptor-γ.
aDepartment of Laboratory Medicine, University of California, San Francisco, USA
bOsaka University Graduate School of Medicine, Osaka, Japan
cInstitute for Clinical and Experimental Medicine, Prague, Czech Republic, USA
dUniversity of Michigan Medical School, Ann Arbor, USA
eSecond Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan
f1st Medical Faculty, Charles University
gInstitute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
Correspondence to Michal Pravenec PhD, Institute of Physiology, Czech Academy of Sciences, Vídeňská 1083, 14220 Prague 4, Czech Republic Tel: +420 241062297; fax: +420 241062488; e-mail: email@example.com