Angiotensin II type 1 receptor-independent beneficial effects of telmisartan on dietary-induced obesity, insulin resistance and fatty liver in mice.
OBJECTIVE
Evidence suggests that telmisartan, an angiotensin II type 1 receptor (AT1) blocker and peroxisome proliferator-activated receptor-gamma partial agonist, has beneficial actions that limit development of the metabolic syndrome and diabetes. However, the role played by AT1 inhibition in metabolic effects elicited by telmisartan remains uncertain. Here we isolated the metabolic effects of telmisartan from AT1 antagonism.


METHODS
Male At1a (also known as Agtr1a)-deficient mice were fed a standard diet or 60% high-fat diet; those on high-fat diet were co-administered telmisartan (3 mg kg(-1) day(-1) by oral gavage) or vehicle for 12 weeks.


RESULTS
In At1a-null mice, telmisartan prevented high-fat-diet-induced increases in (1) body weight, epididymal and inguinal white adipose tissue weight, adipocyte size and plasma leptin concentration; (2) plasma glucose and insulin concentrations and HOMA index; and (3) liver weight and triacylglycerol content. Insulin tolerance testing also indicated that telmisartan improved the high-fat-diet-induced reduction of glucose-lowering by insulin.


CONCLUSIONS
The present findings demonstrate beneficial, AT1-independent effects of the AT1 blocker telmisartan on dietary-induced obesity, insulin resistance and fatty liver in animals.
Rong
X
X
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Li
Y
Y
Ebihara
K
K
Zhao
M
M
Naowaboot
J
J
Kusakabe
T
T
Kuwahara
K
K
Murray
M
M
Nakao
K
K
D017667:Adipocytes / Q000473:pathology; D052436:Adipose Tissue, White / Q000473:pathology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D001786:Blood Glucose / Q000032:analysis; D048429:Cell Size; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry; D056128:Obesity, Abdominal / Q000188:drug therapy* / Q000209:etiology; D009929:Organ Size; D047495:PPAR gamma / Q000819:agonists; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency / Q000502:physiology*; D000077333:Telmisartan; D014280:Triglycerides / Q000032:analysis
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D014280:Triglycerides; D000077333:Telmisartan
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