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Hypothalamic Ceramide Levels Regulated by CPT1C Mediate the Orexigenic Effect of Ghrelin

Overview of attention for article published in Diabetes, June 2013
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Title
Hypothalamic Ceramide Levels Regulated by CPT1C Mediate the Orexigenic Effect of Ghrelin
Published in
Diabetes, June 2013
DOI 10.2337/db12-1451
Pubmed ID
Authors

Sara Ramírez, Luís Martins, Jordi Jacas, Patricia Carrasco, Macarena Pozo, Josep Clotet, Dolors Serra, Fausto G. Hegardt, Carlos Diéguez, Miguel López, Núria Casals

Abstract

Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). However, it is unclear whether the brain-specific isoform CPT1C, which is located in the endoplasmic reticulum of neurons, may play a role in this action. Here, we demonstrate that the orexigenic action of ghrelin is totally blunted in CPT1C knockout (KO) mice, despite having the canonical ghrelin signaling pathway activated. We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0 ceramide levels mediated by CPT1C. Notably, central inhibition of ceramide synthesis with myriocin negated the orexigenic action of ghrelin and normalized the levels of AgRP and NPY, as well as their key transcription factors phosphorylated cAMP-response element-binding protein and forkhead box O1. Finally, central treatment with ceramide induced food intake and orexigenic neuropeptides expression in CPT1C KO mice. Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 2 2%
Mexico 1 1%
Unknown 80 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 20%
Researcher 15 18%
Student > Master 9 11%
Professor > Associate Professor 6 7%
Student > Doctoral Student 5 6%
Other 15 18%
Unknown 16 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 26 31%
Biochemistry, Genetics and Molecular Biology 16 19%
Medicine and Dentistry 10 12%
Neuroscience 4 5%
Nursing and Health Professions 3 4%
Other 6 7%
Unknown 18 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 September 2013.
All research outputs
#15,273,442
of 22,712,476 outputs
Outputs from Diabetes
#7,600
of 9,198 outputs
Outputs of similar age
#122,932
of 197,992 outputs
Outputs of similar age from Diabetes
#81
of 120 outputs
Altmetric has tracked 22,712,476 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,198 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.1. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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We're also able to compare this research output to 120 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.