Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha.
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.
Chiellini
Chiara
C
Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
Bertacca
Anna
A
Novelli
Silvia E
SE
Görgün
Cem Z
CZ
Ciccarone
Annamaria
A
Giordano
Antonio
A
Xu
Haiyan
H
Soukas
Alexander
A
Costa
Mario
M
Gandini
Daniele
D
Dimitri
Roberto
R
Bottone
Pietro
P
Cecchetti
Paolo
P
Pardini
Ennia
E
Perego
Lucia
L
Navalesi
Renzo
R
Folli
Franco
F
Benzi
Luca
L
Cinti
Saverio
S
Friedman
Jeffrey M
JM
Hotamisligil
Gökhan S
GS
Maffei
Margherita
M
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
D006242:Haptoglobins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha