AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

Abstract

Obesity is a chronic metabolic condition with important public health implications associated with numerous co-morbidities including cardiovascular disease, insulin resistance, and hypertension. The renin angiotensin system (RAS), best known for its involvement in cardiovascular control and body fluid homeostasis has, more recently, been implicated in regulation of energy balance. Interference with the RAS (genetically or pharmacologically) has been shown to influence body weight gain. In this study we investigated the effects of systemic AT1 receptor blockade using losartan on ingestive behaviors and weight gain in diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day) body weight gain remained constant within the DIO animals (3.6 ± 0.3 g/day, n = 8), diet resistant (DR) animals (2.1 ± 0.6 g/day, n = 8) and in the age-matched chow fed control (CHOW) animals (2.8 ± 0.3 g/day, n = 8), Losartan administration abolished body weight gain in animals fed a high fat diet (DIO: -0.4 ± 0.7 g/day, n = 8; and DR: -0.8 ± 0.3 g/day, n = 8) while chow fed animals continued to gain weight (2.2 ± 0.3 g/day, n = 8) as they had previously to oral administration of losartan. This decrease in daily body weight gain was accompanied by a decrease in food intake in the HFD fed animals. Following the removal of losartan, both the DIO and DR animals again showed daily increases in body weight gain and food intake which were similar to control values. Our data demonstrate that oral losartan administration attenuates body weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR while having no effect on body weight gain in age-matched chow fed animals suggesting a protective effect of losartan against body weight gain while on a HFD.

Interactive effects of oligofructose and obesity predisposition on gut hormones and microbiota in diet‐induced obese rats

“…The reason for the divergence in adiposity gains between prone and resistant rodents is not known but can be partially explained by increased energy intake and the development of resistance to the actions of leptin, a key regulator of food intake and energy metabolism . Recently, it was shown that losartan, a systemic AT 1 receptor blocker, similarly reduced body weight in rats fed a high‐fat diet whether they were DIO or DR . We also previously showed that the neutral cannabinoid CB 1 receptor antagonist AM4113 reduced body weight that rapidly stabilized at 5 and 10% less than vehicle‐treated rats respectively with a 2 and 10 mg/kg dose .…”

Bloqueio do receptor AT1 da Angiotensina II reduz o número de folículos antrais em ratas com obesidade induzida por dieta de cafeteria

“…Esses resultados são concordantes com os de estudos prévios que mostram que o tratamento com antagonistas do receptor AT 1 da Angiotensina II é benéfico contra a obesidade e a resistência à insulina 8,12 . Todavia, não alterou o peso da gordura perigonadal das fê-meas obesas, postulando efeitos tecido-específico dessa droga.…”

Sex‐specific differences in cardiovascular and metabolic hormones with integrated signalling in the paraventricular nucleus of the hypothalamus

“…Similar to its effects on blood pressure, losartan has also been shown to attenuate body weight gain in obese and diet-resistant rats fed a high-fat diet (Smith et al 2014). Paraventricular nucleus AT 1a knockout mice fed a high-fat diet have increased adiposity attributable to both increased energy consumption and decreased energy expenditure (de Kloet et al 2013).…”