Chronic blockade of angiotensin AT₁ receptors improves cardinal symptoms of metabolic syndrome in diet-induced obesity in rats

Br J Pharmacol. 2014 Feb;171(3):746-60. doi: 10.1111/bph.12510.


Background and purpose: 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.

Experimental approach: 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.

Key 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 and implications: 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.

Keywords: AT1-receptor blockade; leptin resistance; metabolic syndrome; obesity; rat; telmisartan; weight loss.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amlodipine / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Anti-Obesity Agents / therapeutic use*
  • Antihypertensive Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Benzimidazoles / therapeutic use*
  • Benzoates / therapeutic use*
  • Diet, High-Fat / adverse effects
  • Dietary Sucrose / adverse effects
  • Drug Therapy, Combination
  • Energy Intake / drug effects
  • Hyperlipidemias / etiology
  • Hyperlipidemias / prevention & control
  • Hypertension / etiology
  • Hypertension / prevention & control
  • Hypolipidemic Agents / therapeutic use
  • Insulin Resistance*
  • Leptin / blood
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / physiopathology
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / etiology
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Telmisartan
  • Weight Gain / drug effects


  • Angiotensin II Type 1 Receptor Blockers
  • Anti-Obesity Agents
  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Dietary Sucrose
  • Hypolipidemic Agents
  • Leptin
  • Amlodipine
  • Telmisartan