Cited by 57Regulation of Appetite and ObesityPeroxisome Proliferator-Activated ReceptorsPharmacology and Obesity Treatment

C75 is converted to C75-CoA in the hypothalamus, where it inhibits carnitine palmitoyltransferase 1 and decreases food intake and body weight

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Mera, Paula, Bentebibel, Assia, López-Viñas, Eduardo, Cordente, Antonio G., Gurunathan, Chandrashekaran, Sebastián, David, Vázquez, Irene, Herrero, Laura +6 more·2009·Biochemical Pharmacology

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.

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Crossref · 10.1016/j.bcp.2008.11.020

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  • Pharmacological and genetic inhibition of hypothalamic CPT1A has been reported to reduce food intake.

    “Even so, in the last decade, pharmacological and genetic inhibition of hypothalamic CPT1A has been reported to reduce the food intake ([10](#B10), [110](#B110), [127](#B127)), potentially as a result of LCFA-CoA cytoplasmic accumulation.”

    From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [110]

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Authors
Mera, P., Bentebibel, A., López-Viñas, E., Cordente, A. G., Gurunathan, C., Sebastián, D., Vázquez, I., Herrero, L., Ariza, X., Gómez-Puertas, P., Asins, G., Serra, D., García, J., & Hegardt, F. G.
Affiliations
  • Instituto de Salud Carlos III (ES)
  • Institut de Biomedicina de la Universitat de Barcelona (ES)
Corresponding author
Hegardt, Fausto G.
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2009-03
Volume
77
Issue
6
Pages
1084-1095
ISSN
0006-2952 (ISSN-L)
OpenAlex
W2150320605
Cited by
57
References
50
Citations by year
2026: 1 · 2025: 2 · 2024: 7 · 2023: 9 · 2021: 1 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 7 · 2012: 5
FWCI
1.78
Type
journal article
Language
en
Open access
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
C75, carnitine palmitoyltransferase 1, fatty acid oxidation, hypothalamus, dietary intake, body weight, obesity, type 2 diabetes, hypophagia, enzyme inhibition
MeSH terms
Acyl Coenzyme A, Animals, Binding Sites, Body Weight, Carnitine O-Palmitoyltransferase, Eating, Female, Humans, Hypothalamus, 4-Butyrolactone, Weight Loss, Rats, Sprague-Dawley, Protein Structure, Secondary, Mice, Rats

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