Inhibition of Angiotensin Converting Enzyme Induces Beige Adipocytes through Angiotensin‐(1–7) in 3T1‐L1 Adipocytes and Obese Mice

Abstract

The renin angiotensin system (RAS) has recently been recognized as an important factor in the regulation of energy balance. Adipocytes express all the components of renin angiotensin system (RAS), including Angiotensin‐(1–7) [Ang‐(1–7)] and Mas receptors. Ang‐(1–7), through Mas receptors, induces PPARy expression in 3T3‐L1 adipocytes and releases nitric oxide (NO) in diverse cells. White adipose tissue differentiates to beige adipose tissue through PPARy and NO stimulates mitochondrial biogenesis in brown adipose tissue (BAT). In recent years, beige adipocytes have been found, and they have some similar characteristics of BAT including a high thermogenic capacity due to a higher content of mitochondria and uncoupling protein 1 (UCP1). An increase of beige adipocytes has been associated with beneficial effects in health preventing obesity. The aim of this work is to determine if Ang‐(1–7) induces beige adipocytes in 3T3‐L1 cells and in high fat diet (HFD) mice. Captopril was used as a pharmacological strategy to increase Ang‐(1–7) concentrations. 3T3.L1 adipocytes were incubated with 3.16 μM of captopril during the maturation phase and then brown‐like genes and beige genes were measured by real‐time PCR. C57BL/6 mice were fed with a HFD for 24 weeks and captopril was administrated during the last four weeks in drinking water (5 mg/kg/day). Body weight, body composition, glucose tolerance test, cold resistance and energy expenditure were measured. Plasma Ang‐(1–7) was quantified with capilar electrophoresis and nitric oxide thorugh Griess reaction. Captopril increased the expression of UCP1 and beige marker genes in 3T3‐L1 adipocytes. In obese HFD‐mice, treatment with captopril reduced weight gain and decreased fat mass continuosly during the four weeks, although food intake was reduced only the first week, there was no change in remaining weeks. Moreover, HFD captopril‐treated group had improved glucose tolerance, increased energy expenditure and had an increase resistance to cold temperatures compared with the HFD group. On the other hand, HFD captopril‐treated group had increased plasma concentrations of Ang(1–7) and nitric oxide. In conclution, Ang‐(1–7) may be a new factor that induces browning process and partly explains the beneficial effects of ACE inhibitors in glucose and energy homeostasis.Support or Funding InformationCONACYT