title: Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha.
abstract: Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals. Hp is a glycoprotein induced by a number of cytokines, LPS (Lipopolysaccharide), and more generally by inflammation. A significant upregulation of WAT Hp expression was also evident in several experimental obese models including the yellow agouti (/) A(y), ob/ob and goldthioglucose-treated mice (10-, 8-, and 7-fold, respectively). To identify the potential signals for an increase in Hp expression in obesity, we examined leptin and TNFalpha in vivo. Wild type animals treated with recombinant leptin did not show any alteration in WAT Hp expression compared to controls that were food restricted to the level of intake of the treated animals. On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue. Finally, a significant downregulation of WAT Hp mRNA was observed in ob/ob mice deficient in TNFalpha function, when compared to the ob/ob controls. These results demonstrate that haptoglobin expression in WAT is increased in obesity in rodents and TNFalpha is an important signal for this regulation.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Chiellini
authors.forename: Anna
authors.initials: A
authors.lastname: Bertacca
authors.forename: Silvia E
authors.initials: SE
authors.lastname: Novelli
authors.forename: Cem Z
authors.initials: CZ
authors.lastname: Görgün
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ciccarone
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Alexander
authors.initials: A
authors.lastname: Soukas
authors.forename: Mario
authors.initials: M
authors.lastname: Costa
authors.forename: Daniele
authors.initials: D
authors.lastname: Gandini
authors.forename: Roberto
authors.initials: R
authors.lastname: Dimitri
authors.forename: Pietro
authors.initials: P
authors.lastname: Bottone
authors.forename: Paolo
authors.initials: P
authors.lastname: Cecchetti
authors.forename: Ennia
authors.initials: E
authors.lastname: Pardini
authors.forename: Lucia
authors.initials: L
authors.lastname: Perego
authors.forename: Renzo
authors.initials: R
authors.lastname: Navalesi
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
authors.forename: Luca
authors.initials: L
authors.lastname: Benzi
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
authors.forename: Margherita
authors.initials: M
authors.lastname: Maffei
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice / Q000235:genetics; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D006242:Haptoglobins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha