The role of T-bet in obesity: lack of T-bet causes obesity in male mice.
The association of T helper (Th) 1 cells with obesity is well documented in both animals and humans. The T-box transcription factor (T-bet) is known as the transcription factor that is responsible for the development of Th1 cells. However, the role of T-bet in obesity has never been elucidated. The present study aimed to investigate the regulatory function of T-bet on obesity in mice. Th1 cytokine levels were decreased, whereas Th2 cytokine level and GATA-3 messenger RNA (mRNA) expression were increased in T-bet knockout (KO) mice. T-bet KO male mice induced obesity as a result of increased body weight and food efficiency despite the fact that they feed a control diet. T-bet KO mice have an increase in weight of white adipose tissue and levels of triacylglyceride and low-density lipoprotein cholesterol. Interestingly, the expression levels of energy expenditure-related genes were decreased in T-bet KO mice. Both T-bet KO male and female mice had impaired glucose tolerance. In white adipose tissue, leptin, the increase in peroxisome proliferator receptor-γ and CAAT/enhancer-binding protein α mRNA expressions in T-bet KO mice was more than that in wild-type mice. Furthermore, we found that the level of interleukin (IL)-6 mRNA expression in white adipose tissue was elevated in T-bet KO mice but not IL-1β and tumor necrosis factor-α. IL-6 mRNA expression was increased in adipocyte fraction and stromal vascular fraction in white adipose tissue of T-bet KO mice. Taken together, our results reveal that T-bet may affect obesity through the regulation of IL-6 expression in adipocytes of white adipose tissue.
Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Kyu-Yeob
KY
Kim
Hyun-Ja
HJ
Jeong
Hyung-Min
HM
Kim
D017667:Adipocytes / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D015850:Interleukin-6 / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015430:Weight Gain / Q000235:genetics; D000098815:T-bet Transcription Factor
D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D015850:Interleukin-6; D047495:PPAR gamma; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014409:Tumor Necrosis Factor-alpha