title: Telmisartan increases fatty acid oxidation in skeletal muscle through a peroxisome proliferator-activated receptor-gamma dependent pathway.
abstract: OBJECTIVE
  Telmisartan is an angiotensin II receptor blocker and selective modulator of peroxisome proliferator-activated receptor-gamma 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-gamma antagonist GW9662 (-0.4 +/- 1.8 nmol palmitate/g/h, P < 0.05).
  
  
  CONCLUSIONS
  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-gamma.
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdová
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Qi
authors.forename: Masaya
authors.initials: M
authors.lastname: Hyakukoku
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kren
authors.forename: Miroslava
authors.initials: M
authors.lastname: Simáková
authors.forename: Václav
authors.initials: V
authors.lastname: Zídek
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Kurtz
authors.forename: Michal
authors.initials: M
authors.lastname: Pravenec
mesh_terms: D050154:Adiposity / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D000077333:Telmisartan; D015430:Weight Gain / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D005227:Fatty Acids; D047495:PPAR gamma; D019808:Losartan; D000077333:Telmisartan