scholarly journals Ghrelin: a hormone regulating food intake and energy homeostasis

2006 ◽  
Vol 96 (2) ◽  
pp. 201-226 ◽  
Author(s):  
Mercedes Gil-Campos ◽  
Concepción María Aguilera ◽  
Ramón Cañete ◽  
Angel Gil
Keyword(s):  
Food Intake ◽  
Regulatory Networks ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Growth Hormone Secretagogue ◽  
Orexigenic Peptide ◽  
Acyl Ghrelin ◽  
Amp Activated Protein Kinase ◽  
Agouti Related Protein

Regulation of energy homeostasis requires precise coordination between peripheral nutrient-sensing molecules and central regulatory networks. Ghrelin is a twenty-eight-amino acid orexigenic peptide acylated at the serine 3 position mainly with an n-octanoic acid, which is produced mainly in the stomach. It is the endogenous ligand of the growth hormone secretagogue (GHS) receptors. Since plasma ghrelin levels are strictly dependent on recent food intake, this hormone plays an essential role in appetite and meal initiation. In addition, ghrelin is involved in the regulation of energy homeostasis. The ghrelin gene is composed of four exons and three introns and renders a diversity of orexigenic peptides as well as des-acyl ghrelin and obestatin, which exhibit anorexigenic properties. Ghrelin stimulates the synthesis of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus neurons of the hypothalamus and hindbrain, which in turn enhance food intake. Ghrelin-expressing neurons modulate the action of both orexigenic NPY/AgRP and anorexigenic pro-opiomelanocortin neurons. AMP-activated protein kinase is activated by ghrelin in the hypothalamus, which contributes to lower intracellular long-chain fatty acids, and this appears to be the molecular signal for the expression of NPY and AgRP. Recent data suggest that ghrelin has an important role in the regulation of leptin and insulin secretion and vice versa. The present paper updates the effects of ghrelin on the control of energy homeostasis and reviews the molecular mechanisms of ghrelin synthesis, as well as interaction with GHS receptors and signalling. Relationships with leptin and insulin in the regulation of energy homeostasis are addressed.

scholarly journals Neither Agouti-Related Protein nor Neuropeptide Y Is Critically Required for the Regulation of Energy Homeostasis in Mice

2002 ◽  
Vol 22 (14) ◽  
pp. 5027-5035 ◽  
Author(s):  
Su Qian ◽  
Howard Chen ◽  
Drew Weingarth ◽  
Myrna E. Trumbauer ◽  
Dawn E. Novi ◽  
...  
Keyword(s):  
Body Weight ◽  
Neuropeptide Y ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Body Weight Gain ◽  
Physiological Role ◽  
Related Protein ◽  
Double Knockout ◽  
Orexigenic Peptide ◽  
Agouti Related Protein

ABSTRACT Agouti-related protein (AgRP), a neuropeptide abundantly expressed in the arcuate nucleus of the hypothalamus, potently stimulates feeding and body weight gain in rodents. AgRP is believed to exert its effects through the blockade of signaling by α-melanocyte-stimulating hormone at central nervous system (CNS) melanocortin-3 receptor (Mc3r) and Mc4r. We generated AgRP-deficient (Agrp−/− ) mice to examine the physiological role of AgRP. Agrp−/− mice are viable and exhibit normal locomotor activity, growth rates, body composition, and food intake. Additionally, Agrp−/− mice display normal responses to starvation, diet-induced obesity, and the administration of exogenous leptin or neuropeptide Y (NPY). In situ hybridization failed to detect altered CNS expression levels for proopiomelanocortin, Mc3r, Mc4r, or NPY mRNAs in Agrp−/− mice. As AgRP and the orexigenic peptide NPY are coexpressed in neurons of the arcuate nucleus, we generated AgRP and NPY double-knockout (Agrp−/− ;Npy−/− ) mice to determine whether NPY or AgRP plays a compensatory role in Agrp−/− or NPY-deficient (Npy−/− ) mice, respectively. Similarly to mice deficient in either AgRP or NPY, Agrp−/− ;Npy−/− mice suffer no obvious feeding or body weight deficits and maintain a normal response to starvation. Our results demonstrate that neither AgRP nor NPY is a critically required orexigenic factor, suggesting that other pathways capable of regulating energy homeostasis can compensate for the loss of both AgRP and NPY.

scholarly journals Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats

2013 ◽  
Vol 52 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Yoshihiro Suzuki ◽  
Keiko Nakahara ◽  
Keisuke Maruyama ◽  
Rieko Okame ◽  
Takuya Ensho ◽  
...  
Keyword(s):  
Food Intake ◽  
Mrna Expression ◽  
Arcuate Nucleus ◽  
Peptide Yy ◽  
Weaning Food ◽  
Hypothalamic Arcuate Nucleus ◽  
Pregnancy And Lactation ◽  
Acyl Ghrelin ◽  
Plasma Leptin ◽  
Agouti Related Protein

The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.

scholarly journals Obesity, food intake and exercise: Relationship with ghrelin

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Gul Tiryaki-Sonmez ◽  
Serife Vatansever ◽  
Burcin Olcucu ◽  
Brad Schoenfeld
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Adult Population ◽  
Peptide Hormone ◽  
Adverse Health Outcomes ◽  
General Adult Population ◽  
Orexigenic Peptide ◽  
Term Energy ◽  
Short And Long Term

SummaryObesity, a disorder of body composition, is defined by a relative or absolute excess of body fat. In general adult population, obesity has been associated with a diverse array of adverse health outcomes, including major causes of death such as cancer, diabetes, cardiovascular disease, as well as functional impairment from problems such as osteoarthritis and sleep apnea. Ghrelin is a newly discovered peptide hormone which plays an important role in obesity. It is a powerful, endogenous orexigenic peptide and has a crucial function in appetite regulation, as well as short – and long-term energy homeostasis. In the presence of increased obesity, decreased physical activity, and high food consumption, the relationship between exercise, appetite, food intake and ghrelin levels has important implications. In this review, we discuss the effect of acute and chronic exercise performance on appetite, food intake and ghrelin and their relationships.

scholarly journals Integration of Nutrient Sensing in Fish Hypothalamus

2021 ◽  
Vol 15 ◽  
Author(s):  
José L. Soengas
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Camp Response Element Binding ◽  
Nutrient Sensing ◽  
Future Research ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Homeobox Transcription Factor ◽  
Endocrine Signaling ◽  
Amp Activated Protein Kinase

The knowledge regarding hypothalamic integration of metabolic and endocrine signaling resulting in regulation of food intake is scarce in fish. Available studies pointed to a network in which the activation of the nutrient-sensing (glucose, fatty acid, and amino acid) systems would result in AMP-activated protein kinase (AMPK) inhibition and activation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Changes in these signaling pathways would control phosphorylation of transcription factors cAMP response-element binding protein (CREB), forkhead box01 (FoxO1), and brain homeobox transcription factor (BSX) leading to food intake inhibition through changes in the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opio melanocortin (POMC), and cocaine and amphetamine-related transcript (CART). The present mini-review summarizes information on the topic and identifies gaps for future research.

scholarly journals Mitophagy: Molecular Mechanisms, New Concepts on Parkin Activation and the Emerging Role of AMPK/ULK1 Axis

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Roberto Iorio ◽  
Giuseppe Celenza ◽  
Sabrina Petricca
Keyword(s):  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Mitochondrial Fission ◽  
E3 Ligases ◽  
Physiological Processes ◽  
New Concepts ◽  
Development And Differentiation ◽  
Amp Activated Protein Kinase ◽  
Spatial Specificity

Mitochondria are multifunctional subcellular organelles essential for cellular energy homeostasis and apoptotic cell death. It is, therefore, crucial to maintain mitochondrial fitness. Mitophagy, the selective removal of dysfunctional mitochondria by autophagy, is critical for regulating mitochondrial quality control in many physiological processes, including cell development and differentiation. On the other hand, both impaired and excessive mitophagy are involved in the pathogenesis of different ageing-associated diseases such as neurodegeneration, cancer, myocardial injury, liver disease, sarcopenia and diabetes. The best-characterized mitophagy pathway is the PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent pathway. However, other Parkin-independent pathways are also reported to mediate the tethering of mitochondria to the autophagy apparatuses, directly activating mitophagy (mitophagy receptors and other E3 ligases). In addition, the existence of molecular mechanisms other than PINK1-mediated phosphorylation for Parkin activation was proposed. The adenosine5′-monophosphate (AMP)-activated protein kinase (AMPK) is emerging as a key player in mitochondrial metabolism and mitophagy. Beyond its involvement in mitochondrial fission and autophagosomal engulfment, its interplay with the PINK1–Parkin pathway is also reported. Here, we review the recent advances in elucidating the canonical molecular mechanisms and signaling pathways that regulate mitophagy, focusing on the early role and spatial specificity of the AMPK/ULK1 axis.

scholarly journals The SLC transporter in nutrient and metabolic sensing, regulation, and drug development

2018 ◽  
Vol 11 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Yong Zhang ◽  
Yuping Zhang ◽  
Kun Sun ◽  
Ziyi Meng ◽  
Ligong Chen
Keyword(s):  
Drug Targets ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Nutrient Sensing ◽  
Neurological Dysfunction ◽  
Metabolic Characteristics ◽  
Slc Transporters ◽  
Wide Range ◽  
Slc Transporter

Abstract The prevalence of metabolic diseases is growing worldwide. Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the etiology of various metabolic diseases. Consistent with metabolic characteristics, the top five organs in which SLC transporters are highly expressed are the kidney, brain, liver, gut, and heart. We aim to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets. SLC transporters serve as ‘metabolic gate’ of cells and mediate the transport of a wide range of essential nutrients and metabolites such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation. Furthermore, the human genomic studies have identified that SLC transporters are susceptible or causative genes in various diseases like cancer, metabolic disease, cardiovascular disease, immunological disorders, and neurological dysfunction. Importantly, a number of SLC transporters have been successfully targeted for drug developments. This review will focus on the current understanding of SLCs in regulating physiology, nutrient sensing and uptake, and risk of diseases.

scholarly journals A Central Role for Neuronal Adenosine 5′-Monophosphate-Activated Protein Kinase in Cancer-Induced Anorexia

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5220-5229 ◽  
Author(s):  
Eduardo R. Ropelle ◽  
José R. Pauli ◽  
Karina G. Zecchin ◽  
Mirian Ueno ◽  
Cláudio T. de Souza ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Life Span ◽  
Energy Homeostasis ◽  
Ampk Activation ◽  
Chronic Infusion ◽  
The Central Nervous System ◽  
Amp Activated Protein Kinase ◽  
Oxide Synthase ◽  
Cancer Anorexia

The pathogenesis of cancer anorexia is multifactorial and associated with disturbances of the central physiological mechanisms controlling food intake. However, the neurochemical mechanisms responsible for cancer-induced anorexia are unclear. Here we show that chronic infusion of 5-amino-4imidazolecarboxamide-riboside into the third cerebral ventricle and a chronic peripheral injection of 2 deoxy-d-glucose promotes hypothalamic AMP-activated protein kinase (AMPK) activation, increases food intake, and prolongs the survival of anorexic tumor-bearing (TB) rats. In parallel, the pharmacological activation of hypothalamic AMPK in TB animals markedly reduced the hypothalamic production of inducible nitric oxide synthase, IL-1β, and TNF-α and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis. Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats. Collectively, the findings of this study suggest that hypothalamic AMPK activation reverses cancer anorexia by inhibiting the production of proinflammatory molecules and controlling the neuropeptide expression in the hypothalamus, reflecting in a prolonged life span in TB rats. Thus, our data indicate that hypothalamic AMPK activation presents an attractive opportunity for the treatment of cancer-induced anorexia.

scholarly journals Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation

2015 ◽  
Vol 226 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Farhana Naznin ◽  
Koji Toshinai ◽  
T M Zaved Waise ◽  
Cherl NamKoong ◽  
Abu Saleh Md Moin ◽  
...  
Keyword(s):  
Food Intake ◽  
Inflammatory Responses ◽  
Nodose Ganglion ◽  
Afferent Nerve ◽  
Ghrelin Receptor ◽  
Diet Induced Obesity ◽  
Orexigenic Peptide ◽  
Hypothalamic Arcuate Nucleus ◽  
Vagal Afferent ◽  
Amp Activated Protein Kinase

Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway. Administration (s.c.) of ghrelin did not induce food intake, suppression of oxygen consumption, electrical activity of the vagal afferent nerve, phosphorylation of ERK2 and AMP-activated protein kinase alpha in the nodose ganglion, or Fos expression in hypothalamic arcuate nucleus of mice fed a HFD for 12 weeks. Administration of anti-ghrelin IgG did not induce suppression of food intake in HFD-fed mice. Expression levels of ghrelin receptor mRNA in the nodose ganglion and hypothalamus of HFD-fed mice were reduced. Inflammatory responses, including upregulation of macrophage/microglia markers and inflammatory cytokines, occurred in the nodose ganglion and hypothalamus of HFD-fed mice. A HFD blunted ghrelin signaling in the nodose ganglion via a mechanism involvingin situactivation of inflammation. These results indicate that ghrelin resistance in the obese state may be caused by dysregulation of ghrelin signaling via the vagal afferent.

scholarly journals Hypothalamic Cocaine- and Amphetamine-Regulated Transcript (CART) and Agouti-Related Protein (AgRP) Neurons Coexpress the NOP1 Receptor and Nociceptin Alters CART and AgRP Release

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3526-3534 ◽  
Author(s):  
Gavin A. Bewick ◽  
Waljit S. Dhillo ◽  
Sarah J. Darch ◽  
Kevin G. Murphy ◽  
James V. Gardiner ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Ex Vivo ◽  
Zona Incerta ◽  
Related Protein ◽  
Orphanin Fq ◽  
Anatomical Basis ◽  
Agouti Related Protein

Abstract Nociceptin or orphanin FQ (N/OFQ) and its receptor NOP1 are expressed in hypothalamic nuclei involved in energy homeostasis. N/OFQ administered by intracerebroventricular or arcuate nucleus (ARC) injection increases food intake in satiated rats. The mechanisms by which N/OFQ increases food intake are unknown. We hypothesized that N/OFQ may regulate hypothalamic neurons containing peptides involved in the control of food intake such as cocaine- and amphetamine-regulated transcript (CART), αMSH, neuropeptide Y (NPY), and agouti-related protein (AgRP). We investigated the ability of N/OFQ to alter the release of CART, αMSH, NPY, and AgRP using ex vivo medial basal hypothalamic explants. Incubation of hypothalamic explants with N/OFQ (1, 10, 100 nm) resulted in significant changes in CART and AgRP release. One hundred nanomoles N/OFQ caused a 33% decrease in release of CART (55–102) immunoreactivity (IR) and increased release of AgRP-IR to 163% but produced no change in either αMSH-IR or NPY-IR. Double immunocytochemistry/in situ hybridization demonstrated that CART-IR and NOP1 mRNA are colocalized throughout the hypothalamus, in particular in the paraventricular nucleus, lateral hypothalamus, zona incerta, and ARC, providing an anatomical basis for N/OFQ action on CART release. Dual in situ hybridization demonstrated that AgRP neurons in the ARC also express the NOP1 receptor. Our data suggest that nociceptin via the NOP1 receptor may increase food intake by decreasing the release of the anorectic peptide CART and increasing the release of the orexigenic peptide AgRP.

Sign in / Sign up

Export Citation Format

Share Document