Premium
Effects of 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD) and leptin on hypothalamic mRNA expression of factors participating in food intake regulation in a TCDD‐sensitive and a TCDD‐resistant rat strain
Author(s) -
Lindén Jere,
Korkalainen Merja,
Lensu Sanna,
Tuomisto Jouko,
Pohjanvirta Raimo
Publication year - 2005
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20065
Subject(s) - orexigenic , medicine , endocrinology , leptin , chemistry , wasting syndrome , messenger rna , wasting , biology , neuropeptide y receptor , neuropeptide , obesity , receptor , biochemistry , gene
An acutely toxic dose of 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD) leads to a drastically and permanently reduced feed intake and wasting by an unknown mechanism. We focused on the possible interference of TCDD with hypothalamic factors known to take part in the regulation of eating and metabolism, utilizing the over 1000‐fold TCDD‐sensitivity difference between Long‐Evans ( Turku / AB ; L‐E) and Han/Wistar ( Kuopio ) rats. The mRNA expression of 18 hypothalamic factors (including NPY, AgRP, and CART) was measured by quantitative RT‐PCR at 6, 24 and 96 h after TCDD administration. The effects of TCDD were compared with those of leptin and with feed restriction employing a TCDD dose that elicited a severe reduction of feed intake in L‐E rats. TCDD mainly modified expression of orexigenic factors causing an initial suppression followed by reversal to enhanced expression by 96 h. The latter was also seen in feed‐restricted controls. In contrast, leptin altered both orexigenic and anorexigenic factor mRNAs in a more even manner and its effects were clustered at 6 h. The transient nature of feeding‐promoting factor suppression does not strongly support a key role for this phenomenon in TCDD‐induced wasting syndrome. However, the fact that TCDD mainly affected orexigenic factors and the temporal differences in response found between the rat strains warrant further research. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:139–148, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20065