Importance of TNF-alpha and leptin in obesity and insulin resistance: a hypothesis on the impact of physical exercise.
Obesity is associated with an increased incidence of insulin resistance, dyslipoproteinemia, and hypercoagulability. In a more recently established hypothesis of body weight control and regulation of metabolism, the adipocyte secretes leptin and locally expresses TNF-alpha, the latter being responsible for the expression of metabolic cardiovascular risk factors. TNF-a mRNA expression and TNF-alpha protein are greatly increased in adipose tissue from obese animals and humans. Elevated TNF-alpha expression induces insulin resistance by downregulating the tyrosine kinase activity of the insulin receptor and decreasing the expression of GLUT-4 glucose transporters. TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes. Moreover, adipocytes secrete leptin, a molecule with a secondary cytokine structure whose concentrations correlate with the amount of fat tissue. Increased leptin levels downregulate appetite and increase sympathetic activity and thermogenesis in the hypothalamus. Diet-induced weight loss reduces adipose TNF-alpha expression and serum leptin levels and is associated with improved insulin sensitivity and lipid metabolism. Although exercise has also been shown to reduce leptin levels, an influence on TNF-a expression in adipocytes or muscle cells has not yet been demonstrated.
Halle
M
M
Dept. of Rehabilitation, Prevention, and Sports Medicine, Freiburg University Hospital, Germany.
Berg
A
A
Northoff
H
H
Keul
J
J
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology; D003327:Coronary Disease / Q000276:immunology; D004032:Diet; D015444:Exercise; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin; D009765:Obesity; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*; D015431:Weight Loss
D020738:Leptin; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha