Potential role of TNFalpha and lipoprotein lipase as candidate genes for obesity.
To maintain body weight, metabolic efficiency was promoted during evolution; two candidate genes for body weight regulation are lipoprotein lipase (LPL) and tumor necrosis factor-alpha (TNFalpha). Human fat cells do not synthesize lipid, but rely on LPL-mediated plasma triglyceride hydrolysis. Adipose LPL is elevated in obesity. Following weight loss, LPL is elevated further, suggesting attempts to maintain lipid stores during fasting and to replenish lipid stores during refeeding. Muscle LPL is regulated inversely to adipose LPL. Thus, an increased adipose/muscle LPL ratio would partition dietary lipid into adipose tissue and would explain some of the variability in weight gain when humans are exposed to excess calories. Adipose tissue TNFalpha expression is increased in obese rodents and humans and may be important in obesity. When insulin-resistant rodents were injected with anti-TNF binding protein, insulin action improved, suggesting a link between insulin resistance and TNF. TNF is expressed at higher levels in muscle cells of insulin-resistant subjects, and TNF may inhibit LPL expression. Overall, TNF may function to make the subject less obese by inhibiting LPL and rendering the animal more insulin resistant. Obesity has many components, both metabolic and behavioral. However, the metabolic changes resulting from LPL and TNF likely played a role in regulating body adipose tissue during much of human evolution and continue to affect human obesity today.
Kern
P A
PA
Department of Medicine, University of Arkansas for Medical Sciences and John L. McClellan VA Medical Center, Little Rock, AR 72205, USA.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D008071:Lipoprotein Lipase