Renin-angiotensin system modulation through enalapril and/or exercise training improves visceral adiposity in obese mice

Life Sci. 2022 Feb 15:291:120269. doi: 10.1016/j.lfs.2021.120269. Epub 2021 Dec 30.

Abstract

Introduction: Obesity-related metabolic diseases occur as a result of disruptions in white adipose tissue (WAT) plasticity, especially through visceral fat accumulation and adipocyte hypertrophy. This study aimed to evaluate the impact of renin-angiotensin system (RAS) and bradykinin receptors modulation by enalapril treatment and/or exercise training on WAT morphology and related deleterious outcomes.

Methods: Male C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At the 8th week, HF-fed animals were divided into sedentary (HF), enalapril treatment (HF-E), exercise training (HF-T), and enalapril treatment plus exercise training (HF-ET) groups. Following the experimental protocol, body mass gain, adiposity index, insulin resistance, visceral WAT morphometry, renin-angiotensin system, and bradykinin receptors were evaluated.

Results: The HF group displayed increased adiposity, larger visceral fat mass, and adipocyte hypertrophy, which was accompanied by insulin resistance, overactivation of Ang II/AT1R arm, and favoring of B1R in bradykinin receptors profile. All interventions ameliorated visceral adiposity and related outcomes by favoring the Ang 1-7/MasR arm and the B2R expression in B1R/B2R ratio. However, combined therapy additively reduced Ang II/Ang 1-7 ratio.

Conclusion: Our results suggest that Ang 1-7/MasR arm and B2R activation might be relevant targets in the treatment of visceral obesity.

Keywords: ACE inhibition; bradykinin receptors; exercise training; obesity; renin angiotensin system; visceral adipose tissue.

MeSH terms

  • Adipose Tissue, White / metabolism
  • Adiposity / drug effects
  • Adiposity / physiology
  • Animals
  • Diet, High-Fat
  • Enalapril / metabolism
  • Enalapril / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy
  • Obesity / metabolism
  • Obesity, Abdominal / metabolism
  • Physical Conditioning, Animal / physiology*
  • Receptors, Bradykinin / metabolism
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*

Substances

  • Insulin
  • Receptors, Bradykinin
  • Enalapril