Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity

Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8033-8. doi: 10.1073/pnas.97.14.8033.


Severe quantitative and qualitative brown adipocyte defects are common in obesity. To investigate whether aberrant expression of tumor necrosis factor alpha (TNF-alpha) in obesity is involved in functional brown fat atrophy, we have studied genetically obese (ob/ob) mice with targeted null mutations in the genes encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor alone resulted in a significant reduction in brown adipocyte apoptosis and an increase in beta(3)-adrenoreceptor and uncoupling protein-1 expression in obese mice. Increased numbers of multilocular functionally active brown adipocytes, and improved thermoregulation was also observed in obese animals lacking TNF-alpha function. These results indicate that TNF-alpha plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / drug effects*
  • Animals
  • Antigens, CD / genetics
  • Apoptosis*
  • Body Temperature
  • Carrier Proteins / metabolism
  • Cold Temperature
  • Cyclic AMP / biosynthesis
  • In Situ Nick-End Labeling
  • Ion Channels
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Mutant Strains
  • Mitochondrial Proteins
  • Mutation
  • Obesity / metabolism*
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta-3
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Uncoupling Agents / metabolism
  • Uncoupling Protein 1


  • Antigens, CD
  • Carrier Proteins
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Proteins
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • Ucp1 protein, mouse
  • Uncoupling Agents
  • Uncoupling Protein 1
  • Cyclic AMP