Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain.
Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma agonistic properties. Telmisartan prevents weight gain and decreases food intake in models of obesity and in glitazone-treated rodents. This study further investigates the influence of telmisartan and pioglitazone and their association on weight gain and body composition by examining their influence on neuroendocrine mediators involved in food intake. Male C57/Black 6 mice were fed a high-fat diet, weight matched, and randomized in 4 treatment groups: vehicle, pioglitazone, telmisartan, and pioglitazone-telmisartan. Weight gain, food and water intake, body composition, plasma leptin levels, and the hypothalamic expression of neuroendocrine mediators were analyzed. Additional studies were performed with irbesartan and in angiotensin II 1(A) receptor-knockout mice. Telmisartan abolished weight and fat gain in vehicle- and pioglitazone-treated mice while decreasing food intake, the hypothalamic expression of the agouti-related protein, and plasma leptin levels. Modifications in neuropeptide Y and proopiomelanocortin were not consistent with changes in food intake. The effects on weight gain and expression of the agouti-related protein were intermediate with irbesartan. The effects of telmisartan on weight gain were even more pronounced in angiotensin II 1(A) receptor-knockout mice. This study confirms the anorexigenic effects of telmisartan in mice fed a high-fat diet and suggests for the first time a functional role of telmisartan on hypothalamic orexigenic agouti-related protein regulation. These anorexigenic properties abolish both weight gain and body composition modifications in fat-fed and glitazone-treated mice. The anorexigenic properties are independent from the angiotensin II 1(A) receptor.
Service of Endocrinology, Diabetology and Metabolism, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
Gregory
G
Aubert
Michel
M
Burnier
Abdul
A
Dulloo
Christine
C
Perregaux
Lucia
L
Mazzolai
François
F
Pralong
Anne
A
Zanchi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001835:Body Weight; D004032:Diet; D004327:Drinking Behavior; D005247:Feeding Behavior; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009490:Neurosecretory Systems / Q000187:drug effects*; D000077205:Pioglitazone; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D000077333:Telmisartan; D000077205:Pioglitazone