The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis.

By M. Cowley, Roy G. Smith, S. Diano, Matthias Tschöp, N. Pronchuk, K. Grove, C. Strasburger, M. Bidlingmaier, M. Esterman, M. Heiman and 11 more. Neuron, 2003

1,691 citations recorded by the source corpus.

The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.

Subfields: Endocrine and Autonomic Systems, Nutrition and Dietetics, Physiology

View Paper: https://www.semanticscholar.org/paper/d3e9dde9e331ae5cbfa1d7a00e0d394623953eb2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

1. Roger Cone
2. K. Kangawa
3. M. Kojima
4. S. O’Rahilly
5. Matthias Tschöp
6. J. Elmquist
7. I. S. Farooqi
8. A. Coll

In Nutrition and Dietetics

1. Roger Cone
2. K. Kangawa
3. M. Kojima
4. Matthias Tschöp
5. M. Heiman
6. S. O’Rahilly
7. J. Elmquist
8. I. S. Farooqi

In Physiology

1. K. Kangawa
2. M. Kojima
3. Roger Cone
4. Matthias Tschöp
5. M. Heiman
6. S. O’Rahilly
7. William A. Banks
8. J. Morley

Citations in the corpus

• The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review (2007, background): “On the other hand, ghrelin has an inhibitory effect on POMC neurones and CRH-producing neurones (68).”
• Expression of ghrelin receptor mRNA in the rat and the mouse brain (2006, background): “…sites without immediate access to the blood–brain barrier comes from the observations of ghrelin-producing central neurons (Kojima et al., 1999; Hosoda et al., 2000; Tomasetto et al., 2000; Horvath et al., 2001; Lu et al., 2002; Volante et al., 2002; Cowley et al., 2003; Van Der Lely et al., 2004).”
• Studies on the physiological functions of the melanocortin system. (2006, methodology): “Whole cell patch clamp recordings and a loose cell attached patch method using this system were then developed to demonstrate the responsiveness of these neurons to leptin (70), ghrelin (105), serotonin (131), and PYY (126, 127).”
• Deletion of Ghrelin Impairs neither Growth nor Appetite (2003, background): “It has been suggested that ghrelin signals through neuropeptide Y and agouti-related protein in arcuate hypothalamic nuclei ( 5 , 13).”
• Mitochondrial ROS signaling in organismal homeostasis. (2015, background): “Simultaneously, but independently, the sites of action of the hunger-promoting peripheral hormone, ghrelin (Cowley et al., 2003), revealed virtually complete overlap of ghrelin action in the brain and UCP2 expression.”
• The Influence of Exercise on Cognitive Abilities (2013, neutral): “ing energy balance (38, 184), and intravenous injections of ghrelin given to human subjects increase appetite and energy intake (195).”
• Ghrelin: structure and function. (2005, background): “In addition, a recent study has reported the presence of ghrelin in previously uncharacterized hypothalamic neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei (48).”
• Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. (2004, background): “In addition, ghrelin is thought to be produced in brain centers of energy balance control, and, although present there in very small amounts, brain-derived ghrelin might play an additional role in the regulation of energy homoeostasis (51, 123, 152, 198, 372).”
• Ghrelin controls hippocampal spine synapse density and memory performance (2006, background): “and ghrelin binding sites are present outside of the hypothalamus (in the cerebral corte”
• Critical role for peptide YY in protein-mediated satiation and body-weight regulation. (2006, background): “…nucleus, orexigenic neuropeptide Y/agouti-related protein (NPY/AgRP) and anorexigenic proopiomelanocortin (POMC) neurons respond to gut hormones and adiposity signals (Barsh and Schwartz, 2002; Flier, 2004; Acuna-Goycolea and van den Pol, 2005; Batterham et al., 2002; Cowley et al., 2003).”
• Anatomy and regulation of the central melanocortin system (2005, methodology): “Whole-cell patch-clamp recordings and a loose cell-attached patch method using this system were then developed to characterize the responsiveness of these neurons to leptin and other agent”
• The Hormonal Control of Food Intake (2007, positive): “A new set of ghrelin-positive neurons within the hypothalamus, lying between the dorsal, ventral, paraventricular, and arcuate nuclei, were identified by immunohistochemistry (Cowley et al., 2003).”