LEPTIN REGULATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA, TUMOR-NECROSIS-FACTOR, AND UNCOUPLING PROTEIN-2 EXPRESSION IN ADIPOSE TISSUES

It has previously been reported that intracerebroventricular (ICV) adm inistration of leptin induced adipose tissue apoptosis in addition to influencing lipid metabolism. The objective of the present study was t o determine if the expressions of peroxisome proliferator-activated re ceptor-gamma (PPAR gamma), uncoupling protein-2 (UCP2), and tumor necr osis factor (TNF alpha) were influenced by in vivo leptin treatment. E xpression of PPAR gamma, UCP2, and TNF alpha in epididymal fat tissue was examined by Western immunoblot and in situ immunocytochemical anal ysis after 5 days of ICV leptin treatment. Young and old rats (3 and 8 months old) were treated with or without 5 mu g/d leptin. Leptin trea tment increased PPAR gamma expression by 70-80% (P < 0.01) in both age groups. Leptin treatment decreased the expression of UCP2 (P < 0.01) in young rats, whereas it increased UCP2 expression (P < 0.01) in old rats. Leptin treatment also decreased TNF alpha expression by 40% (P < 0.01) in young rats but did not influence its expression in old rats. The basal level of expression of PPAR gamma was greater in 3-month-ol d rats than in 8-month-old rats. The basal level of UCP2 and TNF alpha expression was not different between the two age groups. These immuno blotting data were further confirmed by in situ immunocytochemical ana lysis. The present study suggests that expression of PPAR gamma may be directly involved in the leptin-induced adipocyte apoptosis signal pa thway, whereas UCP2 and TNF alpha may play roles in the leptin-induced lipolysis process. (C) 1998 Academic Press.