Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies examined the development of ingestive responsiveness to blockade of fatty acid oxidation in rat pups using 2-mercaptoacetate (MA), an inhibitor of mitochondrial acyl-coenzyme A dehydrogenases, or methyl palmoxirate (MP), an inhibitor of carnitine palmitoyltransferase I (CPT-I). Rat pups aged 6, 9, 12, or 15 days of age received an intraperitoneal injection of 0, 100, 200, 400, or 800 mumol/kg MA, and intake of a commercial half-and-half or 15% glucose diet from the floor of test containers was assessed in a 30-min test beginning 1 h after administration of MA. The results demonstrate that, although no dose of MA affected intake of either diet in pups 9 days or younger, low doses of MA increased intake and the highest dose suppressed intake of both diets in pups 12 days of age or older. Physiological measurements indicated that levels of beta-hydroxybutyrate were significantly lower following doses of 400 or 800 mumol/kg MA in 9-, 12-, and 15-day-old pups and that gastric emptying was inhibited in 12 and 15 day olds by 800 mumol/kg MA. Intake of a commercial half-and-half diet from the floor of test containers was also assessed in 12- to 18-day-old rat pups 6.5 h after they received a gavage load of 0, 1.25, 2.5, 5, or 10 mg/kg MP. Unlike MA, MP did not increase intake of a commercial half-and-half diet in rat pups 12 or 15-18 days of age; instead, the highest dose of MP suppressed intake in 15- to 18-day-old pups. The failure of MP to enhance intake in pups at the ages tested is likely related to composition of dam's milk; rat milk is high in medium-chain fatty acids that do not require CPT-I for entry into mitochondria. Thus it is likely that MP does not significantly block fatty acid oxidation in pups at the ages tested. On the other hand, blockade of fatty acid oxidation produced by MA significantly affects intake by 12 days of age, suggesting it may be the first metabolic signal that influences intake in rat pups.
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PMID:Development of independent ingestive responding to blockade of fatty acid oxidation in rats. 937 5

Fatty acid oxidation is thought to play a role in the control of food intake, and a low postprandial oxidation of ingested fat may contribute to the overeating on a high-fat diet. Evidence for a role of fatty acid oxidation in control of food intake is mainly derived from the stimulation of feeding in response to administration of the acyl-CoA-dehydrogenase inhibitor mercaptoacetate (MA) and other inhibitors of fatty acid oxidation in different species (rat, mouse, man). Denervation studies suggest that this "lipoprivic feeding" is related to changes in hepatic fatty acid oxidation. In contrast to the strong case for a feeding stimulatory effect of an inhibition of fatty acid oxidation, the evidence for a feeding suppressive effect of a stimulation of fatty acid oxidation is inconsistent and comparatively weak. Ingestion of medium-chain fatty acids (MCFA) and peripheral administration of substances known to increase fatty acid oxidation, such as the fatty acid synthase inhibitor C75 and beta3-adrenergic agonists, decrease feeding. Yet, these substances also reduce the rats' usual preference for saccharin solution, indicating that the feeding suppressive effect is not only due to a stimulation of fatty acid oxidation. A possible approach to answer the question of whether a stimulation of hepatic fatty acid oxidation enhances satiety is to selectively increase expression and activity of the enzyme CPT 1alpha in the liver. CPT 1alpha transfers long-chain fatty acids in the cytosol from CoA to carnitine, which is the precondition for the entry of long-chain fatty acids into mitochondria and the rate-controlling step in mitochondrial fatty acid oxidation. The generation of rats with inducible, liver-specific overexpression of CPT 1alpha should permit to critically examine the putative contribution of hepatic fatty acid oxidation to the control of food intake.
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PMID:Fatty acid oxidation and control of food intake. 1562 Oct 70