Regulation of Immune Cell Function by PPARs and the Connection with Metabolic and Neurodegenerative Diseases

Int J Mol Sci. 2018 May 25;19(6):1575. doi: 10.3390/ijms19061575.

Abstract

Increasing evidence points towards the existence of a bidirectional interconnection between metabolic disease and neurodegenerative disorders, in which inflammation is linking both together. Activation of members of the peroxisome proliferator-activated receptor (PPAR) family has been shown to have beneficial effects in these interlinked pathologies, and these improvements are often attributed to anti-inflammatory effects of PPAR activation. In this review, we summarize the role of PPARs in immune cell function, with a focus on macrophages and T cells, and how this was shown to contribute to obesity-associated inflammation and insulin resistance, atherosclerosis, and neurodegenerative disorders. We address gender differences as a potential explanation in observed contradictory results, and we highlight PPAR-induced metabolic changes as a potential mechanism of regulation of immune cell function through these nuclear receptors. Together, immune cell-specific activation of PPARs present a promising therapeutic approach to treat both metabolic and neurodegenerative diseases.

Keywords: PPARs; T cells; atherosclerosis; gender; inflammation; macrophages; metabolism; neurodegenerative disease; obesity; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Inflammation
  • Macrophages / immunology*
  • Macrophages / pathology
  • Male
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / immunology*
  • Neurodegenerative Diseases / pathology
  • Obesity / genetics
  • Obesity / immunology*
  • Obesity / pathology
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / immunology*
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Sex Factors
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Peroxisome Proliferator-Activated Receptors
  • Protein Isoforms