Tumor Necrosis Factor α Mediates Apoptosis of Brown Adipocytes and Defective Brown Adipocyte Function in Obesity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 14; pp. 8033 - 8038
• Main Authors: Nisoli, Enzo, Briscini, Luca, Giordano, Antonio, Tonello, Cristina, Wiesbrock, Sarah M., Uysal, K. Teoman, Cinti, Saverio, Carruba, Michele O., Hotamisligil, Gokhan S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05.07.2000; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Adaptation, Physiological; Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipose Tissue, Brown - cytology; Adipose Tissue, Brown - drug effects; Animals; Antigens, CD - genetics; Apoptosis; b3-adrenoreceptors; Biological Sciences; Body Temperature; Body weight; Brown adipocytes; Brown adipose tissue; Carrier Proteins - metabolism; Cold Temperature; Cyclic AMP - biosynthesis; Genetics; In Situ Nick-End Labeling; Insulin; Insulin resistance; Ion Channels; Medical research; Membrane Proteins - metabolism; Messenger RNA; Mice; Mice, Mutant Strains; Mitochondrial Proteins; Mutation; Obesity; 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
• ISSN: 0027-8424; 1091-6490
• 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 α (TNF-α ) 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 β3-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-α function. These results indicate that TNF-α plays an important role in multiple aspects of brown adipose tissue biology and mediates the abnormalities that occur at this site in obesity.