title: Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity.
abstract: 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.
authors.affiliation: Center for Study and Research on Obesity, LITA Vialba, L. Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Nisoli
authors.forename: L
authors.initials: L
authors.lastname: Briscini
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.forename: C
authors.initials: C
authors.lastname: Tonello
authors.forename: S M
authors.initials: SM
authors.lastname: Wiesbrock
authors.forename: K T
authors.initials: KT
authors.lastname: Uysal
authors.forename: S
authors.initials: S
authors.lastname: Cinti
authors.forename: M O
authors.initials: MO
authors.lastname: Carruba
authors.forename: G S
authors.initials: GS
authors.lastname: Hotamisligil
mesh_terms: D000222:Adaptation, Physiological; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis; D001831:Body Temperature; D002352:Carrier Proteins / Q000378:metabolism; D003080:Cold Temperature; D000242:Cyclic AMP / Q000096:biosynthesis; D020287:In Situ Nick-End Labeling; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins; D009154:Mutation; D009765:Obesity / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; C000604372:Ucp1 protein, mouse; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000242:Cyclic AMP