The relationship between the metabolic syndrome and energy-utilization deficit in the pathogenesis of obesity-induced osteoarthritis

Med Hypotheses. 2007;69(4):860-8. doi: 10.1016/j.mehy.2007.01.075. Epub 2007 Mar 21.


We propose that the pathogenesis of obesity-induced osteoarthritis may be explained by the metabolic changes in the striated muscle induced by the interaction of insulin resistance and systemic inflammation in obese individuals with metabolic syndrome being osteoarthritis the latest consequence by the physiological changes seen in the metabolic syndrome. Increased levels of TH1 cytokines are produced by activated macrophages in the presence of an acute or chronic infectious disease and suppress the sensitivity of insulin receptors on the membrane of muscle cell and adipocytes. Both cells are activated by inflammatory cytokines and contribute to enhance acute inflammation and to maintain a state of chronic, low-grade inflammation in apparently healthy obese individuals. The increased number of macrophage in the adipose tissue of obese individuals acts as an amplifier of inflammation. Patients with osteoarthritis and metabolic syndrome frequently are complaining about hotness and recurrent edema of feet and hands. It is probable that hyperinsulinemia in the presence of insulin resistance and inflammation, induce vasodilation through the TNF mediated-iNOS overexpression. Patients with metabolic syndrome express clinically the consequence of a poor uptake, storage and energy expenditure by the muscle and any other insulin dependent tissue and the consequence of high insulin plasma levels are vasodilation and increased protein synthesis. The fatigue and muscle weakness induced by insulin resistance and inflammation in obese patients with metabolic syndrome increase the frequency and the intensity of traumatic events of peripheral or axial joints that result in stretch and breaking of tenoperiosteal junction and abrasive damage of cartilage and therefore in these patients with metabolic syndrome and pro-inflammatory state the reparative process of cartilage and periarticular tissues would be severely modified by the growth factor activity in presence of high levels of insulin.

MeSH terms

  • Cytokines / immunology
  • Energy Metabolism*
  • Humans
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / physiopathology*
  • Models, Biological
  • Obesity / complications*
  • Obesity / physiopathology*
  • Osteoarthritis / etiology*
  • Osteoarthritis / immunology
  • Th1 Cells / immunology


  • Cytokines