Metabolic signals and innate immune activation in obesity and exercise

Exerc Immunol Rev. 2015;21:58-68.


The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities.

Keywords: adipose tissue.; exercise; fatty acids; immune system; inflammation; obesity.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Animals
  • Carrier Proteins / physiology
  • Diet / adverse effects
  • Exercise / physiology*
  • Exercise Therapy
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / toxicity
  • Humans
  • I-kappa B Proteins / physiology
  • Inflammasomes / physiology
  • Inflammation / etiology*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation Mediators / blood
  • Inflammation Mediators / physiology
  • Macrophages / physiology
  • Mice, Knockout
  • Motor Activity / physiology
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / physiology
  • Obesity / epidemiology
  • Obesity / immunology
  • Obesity / metabolism*
  • Obesity / therapy
  • Physical Exertion / physiology
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Pattern Recognition / physiology
  • Sedentary Behavior
  • Signal Transduction / physiology
  • Unfolded Protein Response


  • Carrier Proteins
  • Fatty Acids, Nonesterified
  • I-kappa B Proteins
  • Inflammasomes
  • Inflammation Mediators
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Pattern Recognition
  • NF-KappaB Inhibitor alpha