Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender
Open accessAbstract
The orexigenic effect of ghrelin is mediated by neuropeptide Y (NPY) and agouti‐related protein (AgRP) in the hypothalamic arcuate nucleus (ARC). Recent evidence also indicates that ghrelin promotes feeding through a mechanism involving activation of hypothalamic AMP‐activated protein kinase (AMPK) and inactivation of acetyl‐CoA carboxylase and fatty acid synthase (FAS). This results in decreased hypothalamic levels of malonyl‐CoA, increased carnitine palmitoyltransferase 1 (CPT1) activity, and mitochondrial production of reactive oxygen species. We evaluated whether these molecular events are part of a unique signaling cascade or whether they represent alternative pathways mediating the orexigenic effect of ghrelin. Moreover, we examined the gender dependency of these mechanisms, because recent evidence has proposed that ghrelin orexigenic effect is reduced in female rats. We studied in both genders the effect of ghrelin on the expression of AgRP and NPY, as well as their transcription factors: cAMP response‐element binding protein (CREB and its phosphorylated form, pCREB), forkhead box O1 (FoxO1 and its phosphorylated form, pFoxO1), and brain‐specific homeobox transcription factor (BSX). In addition, to establish a mechanistic link between ghrelin, fatty acid metabolism, and neuropeptides, we evaluated the effect of ghrelin after blockage of hypothalamic fatty acid β oxidation, by using the CPT1 inhibitor etomoxir. Ghrelin‐induced changes in the AMPK‐CPT1 pathway are associated with increased levels of AgRP and NPY mRNA expression through modulation of BSX, pCREB, and FoxO1, as well as decreased expression of endoplasmic reticulum (ER) stress markers in a gender‐independent manner. In addition, blockage of hypothalamic fatty acid β oxidation prevents the ghrelin‐promoting action on AgRP and NPY mRNA expression, also in a gender‐independent manner. Notably, this effect is associated with decreased BSX expression and reduced food intake. Overall, our data suggest that BSX integrates changes in neuronal metabolic status with ARC‐derived neuropeptides in a gender‐independent manner.—Lage, R., Vazquez, M. J., Varela, L., Saha, A. K., Vidal‐Puig, A., Nogueiras, R., Diéguez, C., López, M. Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender. FASEB J . 24, 2670–2679 (2010). www.fasebj.org
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Transcription factors affected by changes in hypothalamic fatty acid oxidation, such as CREB, FoxO1, and BSX, are involved in ghrelin-induced expression of NPY and AgRP.
“Transcription factors affected by changes in hypothalamic FAO, such as CREB, FoxO1, and BSX, are involved in ghrelin-induced expression of NPY and AgRP ([92](#B92)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [92]
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- Authors
- Lage, R., Vázquez, M. J., Varela, L., Saha, A. K., Vidal‐Puig, A., Nogueiras, R., Diéguez, C., & López, M.
- Affiliations
- Universidade de Santiago de Compostela (ES)
- Department of Physiology School of Medicine University of Santiago de Compostela‐Instituto de Investigación Sanitaria Santiago de Compostela (A Coruña) Spain
- Boston Medical Center (US)
- University of Cambridge (GB)
- Corresponding author
- López, Miguel
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-03-24
- Volume
- 24
- Issue
- 8
- Pages
- 2670-2679
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC3230529
- OpenAlex
- W2135897497
- Cited by
- 123
- References
- 65
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 16 · 2012: 20
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Hispana (acceptedVersion)
- Repositorio institucional da Universidade de Santiago de Compostela (University of Santiago de Compostela) (submittedVersion)
- Funders
- Ministerio de Educación de la Nación (BFU2008, RyC‐2007‐00211, RyC‐2008‐02219)
- European Commission (Health‐F2‐2008‐223713, AVP FP7MITIN, LSHM‐CT‐2005‐018734)
- Wellcome Trust
- U.S. Public Health Service (K‐19514, DK‐67509)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, neuropeptide Y, agouti-related protein, hypothalamic arcuate nucleus, FOXO1, CREB, AMPK, fatty acid beta-oxidation, carnitine palmitoyltransferase 1, etomoxir, endoplasmic reticulum stress, dietary intake, sex differences, fatty acid metabolism
- MeSH terms
- Animals, Eating, Fatty Acids, Female, Gene Expression Regulation, Hypothalamus, Male, Nerve Tissue Proteins, Neuropeptide Y, Neuropeptides, Sex Factors, Transcription Factors, Homeodomain Proteins, Rats, Agouti-Related Protein, Ghrelin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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