Mechanisms of obesity-induced metabolic and vascular dysfunctions

Front Biosci (Landmark Ed). 2019 Mar 1;24(5):890-934. doi: 10.2741/4758.

Abstract

Obesity has reached epidemic proportions and its prevalence is climbing. Obesity is characterized by hypertrophied adipocytes with a dysregulated adipokine secretion profile, increased recruitment of inflammatory cells, and impaired metabolic homeostasis that eventually results in the development of systemic insulin resistance, a phenotype of type 2 diabetes. Nitric oxide synthase (NOS) is an enzyme that converts L-arginine to nitric oxide (NO), which functions to maintain vascular and adipocyte homeostasis. Arginase is a ureohydrolase enzyme that competes with NOS for L-arginine. Arginase activity/expression is upregulated in obesity, which results in diminished bioavailability of NO, impairing both adipocyte and vascular endothelial cell function. Given the emerging role of NO in the regulation of adipocyte physiology and metabolic capacity, this review explores the interplay between arginase and NO, and their effect on the development of metabolic disorders, cardiovascular diseases, and mitochondrial dysfunction in obesity. A comprehensive understanding of the mechanisms involved in the development of obesity-induced metabolic and vascular dysfunction is necessary for the identification of more effective and tailored therapeutic avenues for their prevention and treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adipogenesis
  • Adipokines / metabolism
  • Adiponectin / metabolism
  • Adipose Tissue / metabolism
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins / metabolism
  • Animals
  • Arginase / metabolism*
  • Cellular Senescence
  • Cytokines / metabolism
  • Endoplasmic Reticulum Stress
  • GPI-Linked Proteins / metabolism
  • Glucose / metabolism
  • Humans
  • Inflammation
  • Insulin / metabolism
  • Lectins / metabolism
  • Leptin / metabolism
  • Lipid Metabolism
  • Lipocalin-2 / metabolism
  • Metabolic Diseases / metabolism*
  • Mice
  • Mitochondria / pathology
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Nitric Oxide / metabolism*
  • Obesity / metabolism*
  • Rats
  • Resistin / metabolism
  • Retinol-Binding Proteins, Plasma / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Diseases / metabolism*

Substances

  • ANGPTL2 protein, human
  • Adipokines
  • Adiponectin
  • Angiopoietin-Like Protein 2
  • Angiopoietin-like Proteins
  • C1QTNF12 protein, human
  • Cytokines
  • GPI-Linked Proteins
  • ITLN1 protein, human
  • Insulin
  • Lectins
  • Leptin
  • Lipocalin-2
  • RBP4 protein, human
  • Resistin
  • Retinol-Binding Proteins, Plasma
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nicotinamide Phosphoribosyltransferase
  • Arginase
  • Glucose