Melatonin inhibits fatty acid transport in inguinal fat pads of hepatoma 7288CTC-bearing and normal Buffalo rats via receptor-mediated signal transduction.
Melatonin inhibits fatty acid uptake and linoleic acid-dependent growth in hepatoma 7288CTC in vivo in Buffalo rats. In this study we measured the effects of melatonin on arteriovenous differences for fatty acids across inguinal fat pads in fed and fasted rats to determine if fatty acid transport in white adipose tissue was also affected by melatonin. Intravenous infusion of melatonin in fasted tumor-bearing rats in vivo simultaneously and rapidly inhibited both fatty acid release from fat pads and fatty acid uptake by the tumors. Perfusion of fat pads in situ in normal rats with melatonin (0.1 nM) inhibited fatty acid release (fasted rats) and uptake (fed rats). Fatty acid transport was restored by addition of any of the following: a melatonin receptor antagonist (S 20928, 1.0 nM), pertussis toxin (0.5 microg/ml), forskolin (1 microM) or 8-Br-cAMP (10 microM). We conclude that fatty acid transport in inguinal fat pads requires cAMP and that melatonin inhibits this transport via a melatonin receptor-mediated, Gi protein-coupled signal transduction pathway. Melatonin has both anticachectic and lipid homeostatic actions in the white adipose tissue of inguinal fat pads.
Sauer
L A
LA
Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, Cooperstown, NY 13326-1394, USA. lensauer@juno.com
Dauchy
R T
RT
Blask
D E
DE
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002940:Circadian Rhythm; D005576:Colforsin / Q000494:pharmacology; D019787:Linoleic Acid / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D009368:Neoplasm Transplantation; D037342:Pertussis Toxin; D051381:Rats; D011915:Rats, Inbred BUF; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D044094:Receptors, Melatonin; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009281:Naphthalenes; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D010566:Virulence Factors, Bordetella; C106874:N-(2-(1-naphthalenyl)ethyl)cyclobutanecarboxamide; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019787:Linoleic Acid; D037342:Pertussis Toxin; D008550:Melatonin