Angiotensin-(1-7) induces beige fat thermogenesis through the Mas receptor

Abstract

a component of the renin angiotensin system, is a vasodilator that exerts its effects primarily through the Mas receptor. The discovery of the Mas receptor in white adipose tissue (WAT) suggests an additional role for this peptide. The aim of the present study was to assess whether Ang-(1-7) can induce the expression of thermogenic genes in white adipose tissue and increase mitochondrial respiration in adipocytes. Materials/methods: Stromal Vascular fraction (SVF)-derived from mice adipose tissue was stimulated for one week with Ang-(1-7), then expression of beige markers and mitochondrial respiration were assessed. Mas +/+ and Mas −/− mice fed a control diet or a high fat-sucrose diet (HFSD) were exposed to a short or long term infusion of Ang-(1-7) and body weight, body fat, energy expenditure, cold resistance and expression of beige markers were assessed. Also, transgenic rats overexpressing Ang-(1-7) were fed with a control diet or a high fat-sucrose diet and the same parameters were assessed. Ang-(1-7) circulating levels from human subjects with different body mass index (BMI) or age were measured. Results: Incubation of adipocytes derived from SVF with Ang-(1-7) increased the expression of beige markers. Infusion of Ang-(1-7) into lean and obese Mas +/+ mice also induced the expression of Ucp1 and some beige markers, an effect not observed in Mas −/− mice. Mas −/− mice had increased body weight gain and decreased cold resistance, whereas rats overexpressing Ang-(1-7) showed the opposite effects. Overexpressing rats exposed to cold developed new thermogenic WAT in the anterior interscapular area. Finally, in human subjects the higher the BMI, low circulating concentration of Ang-(1-7) levels were detected. Similarly, the circulating levels of Ang-(1-7) peptide were reduced with age. Conclusion: These data indicate that Ang-(1-7) stimulates beige markers and thermogenesis via the Mas receptor, and this evidence suggests a potential therapeutic use to induce thermogenesis of WAT, particularly in obese subjects that have reduced circulating concentration of Ang-(1-7).

Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice

“…Ang II elicits exaggerated responses in aged animals, however, due to the increased tissue production of Ang II and the expression of AT1R [ 7 , 26 , 28 , 29 ]. In addition to increased Ang II actions, emerging studies suggest that circulating Ang-(1-7) levels are reduced with aging in human subjects, expression of Mas receptors and ACE2 are decreased in aorta of aged mice, and there is loss of vasodilatory responses to Ang-(1-7) in aorta of aged female mice [ 25 , 26 , 27 ]. This increased Ang II activity combined with decreased protective effects of Ang-(1-7) pathways can contribute to an increase in reactive oxygen species, mitochondrial dysfunction, and end-organ damage in aging [ 7 , 30 ].…”

Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy

“…Indirect calorimetry. Scans were performed as previously described 63 . Fat and lean mass compositions were expressed as delta percentages against basal measurements at day 0.…”

“…On days 0 and 21, and before body composition experiments, an intraperitoneal injection of a 2 g glucose/kg body weight solution was performed per mouse, under an 8 h-period of fasting. Tail-nick blood samples and glucose measurements were prepared as previously described 63 . Glucose measurements were expressed as delta blood glucose concentrations against basal quantification at time 0.…”

“…RNA (3000 ng) was converted to cDNA through reverse transcription. Quantitative real-time polymerase chain reaction was conducted as described before 63 in order to assess the expression of CITED1, TBX1, PPARγ, and UCP1. The primers sequences are found on Supplementary Table S4.…”

The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin–Angiotensin Pathways

“…Emerging reports, however, describe potential heterodimerization and functional interactions between MasR and AT 1 R, AT 2 R, bradykinin B2, endothelin B, and dopamine D2 receptors [54,55]. In animal models and clinical populations, circulating angiotensin-(1-7) levels appear reduced with obesity, suggesting deficiency of this protective hormone [56][57][58]. Chronic restoration of angiotensin-(1-7), both peripherally and centrally, lowers blood pressure and improves insulin sensitivity, glucose tolerance, and lipid metabolism in rodent models of obesity and metabolic syndrome [52].…”