Induction of rat uncoupling protein-2 gene treated with tumour necrosis factor alpha in vivo.
BACKGROUND
The cytokine tumour necrosis factor (TNF) alpha has been reported to induce metabolic abnormalities such as anorexia and thermogenesis. To investigate functional modulators of uncoupling protein-2 (UCP2) gene expression, we examined the effects of TNF-alpha on UCP2 mRNA expression in rats.


METHODS
Mature male Wistar King A (WKA) rats at 10-11 weeks of age were treated with recombinant human TNF-alpha at a dose of 0.6 nmol 100 g-1 body weight by intraperitoneal administration.


RESULTS
TNF-alpha treatment induced an increase in UCP2 mRNA expression in broadly distributed tissues including brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle, and an elevation of ob gene mRNA expression in WAT. After the TNF-alpha treatment, an increase in plasma leptin concentration occurred in an ob gene-dependent manner, accompanied by an anorectic effect.


CONCLUSIONS
The present results provide evidence for a new regulatory loop involving TNF-alpha and UCP2, and add novel insights into the regulatory mechanisms of energy homeostasis.
Masaki
T
T
Oita Medical University, Hasama, Japan.
Yoshimatsu
H
H
Kakuma
T
T
Chiba
S
S
Hidaka
S
S
Tajima
D
D
Kurokawa
M
M
Sakata
T
T
D000273:Adipose Tissue / Q000187:drug effects*; D002001:Adipose Tissue, Brown / Q000187:drug effects; D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001831:Body Temperature / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007473:Ion Channels; D020738:Leptin; D008297:Male; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects*; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000378:metabolism*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2