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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-1-31
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pubmed:abstractText |
Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1-56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0363-6119
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pubmed:author |
pubmed-author:AjaSusanS,
pubmed-author:AplascaAndreaA,
pubmed-author:DanielsKhadijaK,
pubmed-author:HyunJaysonJ,
pubmed-author:KemmMatthewM,
pubmed-author:KlemanAmy MAM,
pubmed-author:KuhajdaFrancis PFP,
pubmed-author:LandreeLeslie ELE,
pubmed-author:McFaddenJill MJM,
pubmed-author:MedghalchiSusan MSM,
pubmed-author:PlummerEricaE,
pubmed-author:RAMONDLL,
pubmed-author:RonnettGabriele VGV,
pubmed-author:ThupariJagan NJN,
pubmed-author:TownsendCraig ACA,
pubmed-author:VadlamudiAravindaA
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pubmed:issnType |
Print
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R352-61
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pubmed:meshHeading |
pubmed-meshheading:18056987-4-Butyrolactone,
pubmed-meshheading:18056987-Animals,
pubmed-meshheading:18056987-Body Weight,
pubmed-meshheading:18056987-Carnitine O-Palmitoyltransferase,
pubmed-meshheading:18056987-Cell Line, Tumor,
pubmed-meshheading:18056987-Dose-Response Relationship, Drug,
pubmed-meshheading:18056987-Eating,
pubmed-meshheading:18056987-Energy Metabolism,
pubmed-meshheading:18056987-Enzyme Activation,
pubmed-meshheading:18056987-Enzyme Inhibitors,
pubmed-meshheading:18056987-Epoxy Compounds,
pubmed-meshheading:18056987-Fatty Acid Synthesis Inhibitors,
pubmed-meshheading:18056987-Fatty Acids,
pubmed-meshheading:18056987-Female,
pubmed-meshheading:18056987-Hypothalamus,
pubmed-meshheading:18056987-Injections, Intraventricular,
pubmed-meshheading:18056987-Male,
pubmed-meshheading:18056987-Mice,
pubmed-meshheading:18056987-Mice, Inbred BALB C,
pubmed-meshheading:18056987-Mice, Inbred C57BL,
pubmed-meshheading:18056987-Neurons,
pubmed-meshheading:18056987-Pregnancy,
pubmed-meshheading:18056987-Rats
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pubmed:year |
2008
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pubmed:articleTitle |
Pharmacological stimulation of brain carnitine palmitoyl-transferase-1 decreases food intake and body weight.
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pubmed:affiliation |
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA. saja1@jhmi.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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