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C75 Is Converted to C75-CoA in the Hypothalamus, Where It Inhibits Carnitine Palmitoyltransferase 1 and Decreases Food Intake and Body Weight

C75 Is Converted to C75-CoA in the Hypothalamus, Where It Inhibits Carnitine Palmitoyltransferase 1 and Decreases Food Intake and Body Weight

Paula Mera, Assia Bentebibel, Eduardo López-Viñas, Antonio G Cordente, Chandrashekaran Gurunathan, David Sebastián, Irene Vázquez, Laura Herrero, Xavier Ariza, Paulino Gómez-Puertas, Guillermina Asins, etc.

Biochem Pharmacol. 2009 Mar 15;77(6):1084-95.

PMID: 19094968

Abstract:

Central nervous system administration of C75 produces hypophagia and weight loss in rodents identifying C75 as a potential drug against obesity and type 2 diabetes. However, the mechanism underlying this effect is unknown. Here we show that C75-CoA is generated chemically, in vitro and in vivo from C75 and that it is a potent inhibitor of carnitine palmitoyltranferase 1 (CPT1), the rate-limiting step of fatty-acid oxidation. Three-D docking and kinetic analysis support the inhibitory effect of C75-CoA on CPT1. Central nervous system administration of C75 in rats led to C75-CoA production, inhibition of CPT1 and lower body weight and food intake. Our results suggest that inhibition of CPT1, and thus increased availability of fatty acids in the hypothalamus, contribute to the pharmacological mechanism of C75 to decrease food intake.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP218137861	C75		218137-86-1	Price

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