Prorenin/renin receptor blockade promotes a healthy fat distribution in obese mice

Obesity (Silver Spring). 2016 Sep;24(9):1946-54. doi: 10.1002/oby.21592. Epub 2016 Jul 26.

Abstract

Objective: Administration of the handle region peptide (HRP), a (pro)renin receptor blocker, decreases body weight gain and visceral adipose tissue (VAT) in high-fat/high-carbohydrate (HF/HC) diet-fed mice. The objective of this study was to elucidate potential mechanisms implicated in these observations.

Methods: Mice were given a normal or a HF/HC diet along with saline or HRP for 10 weeks.

Results: In HF/HC-fed mice, HRP increased the expression of several enzymes implicated in lipogenesis and lipolysis in subcutaneous fat (SCF) while the expression of the enzyme implicated in the last step of lipogenesis decreased in VAT. A reduction was also observed in circulating free fatty acids in these animals which was accompanied by normalized adipocyte size in VAT and increased adipocyte size in SCF. ''Beiging'' is the evolution of a white adipose tissue toward a brown-like phenotype characterized by an increased mitochondrial density and small lipid droplets. HRP increased the expression of' "beiging" markers in SCF of HF/HC diet-fed mice.

Conclusions: HRP treatment may favor healthy fat storage in SCF by activating a triglyceride/free fatty acid cycling and "beiging," which could explain the body weight and fat mass reduction.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Adipose Tissue, White / metabolism
  • Animals
  • Diet, High-Fat
  • Fatty Acids, Nonesterified / metabolism
  • Lipogenesis / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / metabolism
  • Prorenin Receptor
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology*
  • Renin / metabolism*
  • Renin-Angiotensin System / physiology*
  • Triglycerides / metabolism

Substances

  • Fatty Acids, Nonesterified
  • Receptors, Cell Surface
  • Triglycerides
  • Renin
  • Prorenin Receptor