Preventing leptin resistance by blocking angiotensin II AT₁ receptors in diet‐induced obese rats

Abstract

Background and Purpose AT1 receptor blockers (ARBs) represent an approach for treating metabolic syndrome due to their potency in reducing hypertension, body weight and onset of type 2 diabetes. The mechanism underlying ARB‐induced weight loss is still unclear. Experimental Approach Leptin resistance tests (LRTs) in diet‐induced obese or lean rats were conducted to determine whether telmisartan (8 mg·kg−1·day−1, 14 days) enhances leptin sensitivity. Phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) staining was performed in hypothalami to determine leptin transport across the blood–brain barrier. Key Results Telmisartin reduced weight gain, food intake and plasma leptin but blood pressure remained unchanged. The 24 h profiles of plasma leptin after saline injections were similar in controls and telmisartan‐treated rats, but after leptin injections were higher in controls and slightly lower in telmisartan‐treated animals. After telmisartan, energy intake during LRT was lower in leptin‐ than in saline‐pretreated rats, but remained unchanged in controls, irrespectively of whether rats received saline or leptin. Leptin minimized the gain in body weight during LRT in telmisartan‐treated rats as compared with saline‐treated animals. pSTAT3 staining was reduced in cafeteria diet‐fed rats as compared with chow‐fed rats but this was normalized by telmisartan. Telmisartin reduced hypothalamic mRNA levels of the orexigenic peptides melanin‐concentrating hormone and prepro‐orexin. Conclusions and Implications Rats fed a cafeteria diet develop leptin resistance after 2 weeks. Leptin sensitivity was preserved by telmisartan treatment even in rats fed a cafeteria diet. This pleiotropic effect is not related to the hypotensive action of telmisartan.

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

“…However, our data support a possible role for central ANG II signaling in SLR, as we have shown that ANG II AT 1A receptors specifically in leptin-sensitive cells are dispensable for BP control, but necessary for RMR control and thus energy balance. The general concept that AT 1 receptors mediate leptin sensitivity is also supported in a recent study by Müller-Fielitz et al (27). In contrast to the effects observed in our studies, it was demonstrated that peripheral treatment with the AT 1 antagonist telmisartan prevented leptin resistance in rats fed a high-calorie/ cafeteria diet (27).…”

Effect of Angiotensin (1-7) on Heart Function in an Experimental Rat Model of Obesity

“…As previously described, CD consisted of commercial chocolate and cookies (62% carbohydrates, 25% fat, 6% protein, 2% fiber). Rats received only one kind of sweet per day (Müller-Fielitz et al, 2015;Schuchard et al, 2015). Furthermore, chocolate and cookie bars were changed daily in a regular manner (Müller-Fielitz et al, 2015;Schuchard et al, 2015).…”

“…Rats received only one kind of sweet per day (Müller-Fielitz et al, 2015;Schuchard et al, 2015). Furthermore, chocolate and cookie bars were changed daily in a regular manner (Müller-Fielitz et al, 2015;Schuchard et al, 2015). The third group were transgenic (TGR) rats, receiving standard chow food (TGR+chow, n = 6).…”

“…In their experimental study Müller-Fielitz et al demonstrated that 19 weeks of high-caloric diet in rats resulted in metabolic syndrome, characterized by obesity, insulin resistance, hyperphagia, hyperlipidaemia and hypertension (Müller-Fielitz et al, 2015).…”

“…However, there is evidence that an association exists between the renin-angiotensin-aldosterone system (RAAS) and a number of cardiac and metabolic disorders (Santos et al, 2005(Santos et al, , 2012Müller-Fielitz et al, 2015).…”