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Ghrelin regulates hypothalamic prolyl carboxypeptidase expression in mice
Jin Kwon Jeong1, Jung Dae Kim, Sabrina Diano
1Program in Integrative Cell Signaling and Neurobiology of Metabolism, New Haven, CT, 06520, USA ; Department of Ob/Gyn & Reproductive Sciences, New Haven, CT, 06520, USA.
Molecular Metabolism
|September 12, 2013
Summary
Fasting and ghrelin increase hypothalamic prolyl carboxypeptidase (PRCP) expression. This ghrelin-mediated PRCP upregulation may reduce melanocortin signaling, impacting energy metabolism regulation.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
Background:
- Hypothalamic Prolyl carboxypeptidase (PRCP) regulates energy metabolism by modulating melanocortin signaling.
- Alpha-melanocyte stimulating hormone (α-MSH) levels are critical for energy balance and are tightly controlled.
Purpose of the Study:
- To investigate the regulation of hypothalamic PRCP expression.
- To determine the role of fasting and ghrelin in PRCP expression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure Prcp mRNA levels.
- Western blotting to assess PRCP protein levels.
- Administration of ghrelin and assessment in ghrelin knockout mice.
Main Results:
- Fasting significantly up-regulates hypothalamic Prcp mRNA and protein.
- Ghrelin administration increases hypothalamic Prcp mRNA expression.
- Ghrelin's effect on PRCP is mediated through its receptor.
Conclusions:
- Ghrelin is a key regulator of hypothalamic PRCP expression.
- Ghrelin-induced PRCP upregulation offers a novel mechanism to decrease melanocortin signaling.
- This pathway contributes to the neuroendocrine control of energy metabolism.
Keywords:
(ARC), Arcuate nucleus(AgRP), Agouti related peptide(CTX), Cortex(DMH), Dorsomedial nucleus(GHS-R), Growth hormone secretagogue receptor(Hcrt), Hypocretin(LH), Lateral hypothalamus(MCH), Melanin concentrating hormone(NPY), Neuropeptide Y(POMC), Proopiomelanocortin(PRCP), Prolyl carboxypeptidase(Prcpgt/gt), Prcp-ablated mice(VMH), Ventromedial nucleus(α-MSH), α-Melanocyte stimulating hormoneAlpha-melanocyte stimulating hormoneFastingGhrelinHypothalamusProlyl carboxypeptidase
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