TY - JOUR
T1 - Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-α
AU - Finck, Brian N.
AU - Johnson, Rodney W.
PY - 2002
Y1 - 2002
N2 - Tumor necrosis factor (TNF)-α stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-α influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-α (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-α-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-α. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J2 metabolite [15-deoxy-Δ12,14-PG J2 (PGJ)] and then exposed to TNF-α Both compounds completely abolished TNF-α-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-α. PGJ treatment markedly blunted the TNF-α-induced increase in leptin, TNF-α, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-α acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-α-induced hyperleptinemia.
AB - Tumor necrosis factor (TNF)-α stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-α influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-α (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-α-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-α. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J2 metabolite [15-deoxy-Δ12,14-PG J2 (PGJ)] and then exposed to TNF-α Both compounds completely abolished TNF-α-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-α. PGJ treatment markedly blunted the TNF-α-induced increase in leptin, TNF-α, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-α acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-α-induced hyperleptinemia.
KW - 15-deoxy-Δ-prostaglandin J
KW - Endocrine-immune interaction
KW - SB-203580
UR - http://www.scopus.com/inward/record.url?scp=0036084889&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036084889&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00569.2001
DO - 10.1152/ajpregu.00569.2001
M3 - Article
C2 - 11959686
AN - SCOPUS:0036084889
SN - 0363-6119
VL - 282
SP - R1429-R1435
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 5 51-5
ER -