Chronic blockade of angiotensin AT₁ receptors improves cardinal symptoms of metabolic syndrome in diet-induced obesity in rats.
OBJECTIVE
AT₁ receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti-obesity effects of these antagonists, given as a treatment after obesity had been established.


METHODS
In spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg⁻¹·d⁻¹) or amlodipine (10 mg·kg⁻¹·d⁻¹; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg⁻¹·d⁻¹; to control for dose-dependency) for 17 weeks. Rats receiving only chow (C(chow)) or CD-fed rats treated with vehicle (C(CD)) served as controls.


RESULTS
The CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD-induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin-induced energy intake was reduced and respiratory ratio was increased compared with C(CD) rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low-density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups.


CONCLUSIONS
Telmisartan exerted anti-obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.
Institute of Experimental and Clinical Pharmacology and Toxicology, partner site Hamburg/Kiel/Lübeck, Lübeck, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Lübeck, Germany.
Helge
H
Müller-Fielitz
Nils
N
Hübel
Martin
M
Mildner
Florian M
FM
Vogt
Jörg
J
Barkhausen
Walter
W
Raasch
D017311:Amlodipine / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D004359:Drug Therapy, Combination; D002149:Energy Intake / Q000187:drug effects; D006949:Hyperlipidemias / Q000209:etiology / Q000517:prevention & control; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D000077333:Telmisartan; D015430:Weight Gain / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D019440:Anti-Obesity Agents; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D019422:Dietary Sucrose; D000960:Hypolipidemic Agents; D020738:Leptin; D017311:Amlodipine; D000077333:Telmisartan
AT1-receptor blockade; leptin resistance; metabolic syndrome; obesity; rat; telmisartan; weight loss