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Nature Reviews. Endocrinology Jun 2017Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance... (Review)
Review
Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance that is often due to unlimited access to food and an increasingly sedentary lifestyle on the background of a genetic and epigenetic vulnerability. Our understanding of the humoral and neuronal systems that mediate the control of energy homeostasis has improved dramatically in the past few decades. However, our ability to develop effective strategies to slow the current epidemic of obesity has been hampered, largely owing to the limited knowledge of the mechanisms underlying resistance to the action of metabolic hormones such as leptin and ghrelin. The development of resistance to leptin and ghrelin, hormones that are crucial for the neuroendocrine control of energy homeostasis, is a hallmark of obesity. Intensive research over the past several years has yielded tremendous progress in our understanding of the cellular pathways that disrupt the action of leptin and ghrelin. In this Review, we discuss the molecular mechanisms underpinning resistance to leptin and ghrelin and how they can be exploited as targets for pharmacological management of obesity.
Topics: Animals; Cyclic AMP; Drug Resistance; Energy Metabolism; Ghrelin; Homeostasis; Humans; Hypothalamus; Leptin; Obesity; Receptors, Ghrelin; Receptors, Leptin; Signal Transduction
PubMed: 28232667
DOI: 10.1038/nrendo.2016.222 -
Peptides Feb 2018The a 28-amino acid peptide ghrelin was discovered in 1999 as a growth hormone (GH) releasing peptide. Soon after its discovery, ghrelin was found to increase body... (Review)
Review
The a 28-amino acid peptide ghrelin was discovered in 1999 as a growth hormone (GH) releasing peptide. Soon after its discovery, ghrelin was found to increase body weight and adiposity by acting on the hypothalamic melanocortinergic system. Subsequently, ghrelin was found to exert a series of metabolic effects, overall testifying ghrelin a pleiotropic nature of broad pharmacological interest. Ghrelin acts through the growth hormone secretagogue-receptor (GHS-R), a seven transmembrane G protein-coupled receptor with high expression in the anterior pituitary, pancreatic islets, thyroid gland, heart and various regions of the brain. Among ghrelins numerous metabolic effects are the most prominent the stimulation of appetite via activation of orexigenic hypothalamic neurocircuits and the food-intake independent stimulation of lipogenesis, which both together lead to an increase in body weight and adiposity. Ghrelin effects beyond the regulation of appetite and GH secretion include the regulation of gut motility, sleep-wake rhythm, taste sensation, reward seeking behaviour, and the regulation of glucose metabolism. The latter received recently increasing recognition because pharmacological inhibition of ghrelin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes. In this review we highlight the multifaceted nature of ghrelin and summarize its glucoregulatory action and discuss the pharmacological value of ghrelin pathway inhibition for the treatment of glucose intolerance and type 2 diabetes.
Topics: Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Eating; Ghrelin; Glucose; Humans; Receptors, Ghrelin; Signal Transduction
PubMed: 29412824
DOI: 10.1016/j.peptides.2017.12.015 -
Cell Metabolism Apr 2018Ghrelin, a gastric-derived acylated peptide, regulates energy homeostasis by transmitting information about peripheral nutritional status to the brain, and is essential... (Review)
Review
Ghrelin, a gastric-derived acylated peptide, regulates energy homeostasis by transmitting information about peripheral nutritional status to the brain, and is essential for protecting organisms against famine. Ghrelin operates brain circuits to regulate homeostatic and hedonic feeding. Recent research advances have shed new light on ghrelin's multifaceted roles in cellular homeostasis, which could maintain the internal environment and overcome metaflammation in metabolic organs. Here, we highlight our current understanding of the regulatory mechanisms of the ghrelin system in energy metabolism and cellular homeostasis and its clinical trials. Future studies of ghrelin will further elucidate how the stomach regulates systemic homeostasis.
Topics: Animals; Brain; Energy Metabolism; Ghrelin; Homeostasis; Humans; Mice; Rats; Receptors, Ghrelin
PubMed: 29576534
DOI: 10.1016/j.cmet.2018.02.008 -
Current Opinion in Clinical Nutrition... Nov 2013Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects... (Review)
Review
PURPOSE OF REVIEW
Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recent literature indicates that the functions of ghrelin go well beyond its role as an orexigenic signal. Here, we have reviewed some of the most recent findings on ghrelin and its signalling in animals and humans.
RECENT FINDINGS
Ghrelin regulates glucose homeostasis by inhibiting insulin secretion and regulating gluconeogenesis/glycogenolysis. Ghrelin signalling decreases thermogenesis to regulate energy expenditure. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates bone formation and metabolism by modulating proliferation and differentiation of osteoblasts.
SUMMARY
In addition to ghrelin's effects on appetite and adiposity, ghrelin signalling also plays crucial roles in glucose and energy homeostasis, cardioprotection, muscle atrophy and bone metabolism. These multifaceted roles of ghrelin make ghrelin and GHS-R highly attractive targets for drug development. Ghrelin mimetics may be used to treat heart diseases, muscular dystrophy/sarcopenia and osteoporosis; GHS-R antagonists may be used to treat obesity and insulin resistance.
Topics: Animals; Appetite; Cell Differentiation; Cell Proliferation; Energy Metabolism; Ghrelin; Glucose; Growth Hormone; Homeostasis; Humans; Hunger; Insulin; Insulin Secretion; Models, Animal; Muscular Atrophy; Myocytes, Cardiac; Obesity; Osteoblasts; Osteogenesis
PubMed: 24100676
DOI: 10.1097/MCO.0b013e328365b9be -
Biochimica Et Biophysica Acta. Reviews... Aug 2017Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original... (Review)
Review
Ghrelin is a small peptide with 28 amino acids, and has been characterized as the ligand of the growth hormone secretagogue receptor (GHSR). In addition to its original function in stimulating pituitary growth hormone release, ghrelin is multifunctional and plays a role in the regulation of energy balance, gastric acid release, appetite, insulin secretion, gastric motility and the turnover of gastric and intestinal mucosa. The discovery of ghrelin and GHSR expression beyond normal tissues suggests its role other than physiological function. Emerging evidences have revealed ghrelin's function in regulating several processes related to cancer progression, especially in metastasis and proliferation. We further show the relative GHRL and GHSR expression in pan-cancers from The Cancer Genome Atlas (TCGA), suggesting the potential pathological role of the axis in cancers. This review focuses on ghrelin's biological function in cancer progression, and reveals its clinical significance especially the impact on cancer patient outcome.
Topics: Animals; Disease Progression; Energy Metabolism; Ghrelin; Growth Hormone; Humans; Neoplasms; Receptors, Ghrelin
PubMed: 28238732
DOI: 10.1016/j.bbcan.2017.02.002 -
Biomolecules Mar 2022Ghrelin and obestatin are two "sibling proteins" encoded by the same preproghrelin gene but possess an array of diverse and complex functions. While there are ample... (Review)
Review
Ghrelin and obestatin are two "sibling proteins" encoded by the same preproghrelin gene but possess an array of diverse and complex functions. While there are ample literature documenting ghrelin's functions, the roles of obestatin are less clear and controversial. Ghrelin and obestatin have been perceived to be antagonistic initially; however, recent studies challenge this dogma. While they have opposing effects in some systems, they function synergistically in other systems, with many functions remaining debatable. In this review, we discuss their functional relationship under three "C" categories, namely complex, complementary, and contradictory. Their functions in food intake, weight regulation, hydration, gastrointestinal motility, inflammation, and insulin secretion are complex. Their functions in pancreatic beta cells, cardiovascular, muscle, neuroprotection, cancer, and digestive system are complementary. Their functions in white adipose tissue, thermogenesis, and sleep regulation are contradictory. Overall, this review accumulates the multifaceted functions of ghrelin and obestatin under both physiological and pathological conditions, with the intent of contributing to a better understanding of these two important gut hormones.
Topics: Adipose Tissue, White; Ghrelin; Insulin Secretion
PubMed: 35454106
DOI: 10.3390/biom12040517 -
Nutrients Oct 2022Ghrelin, an endogenous brain-gut peptide, is secreted in large quantities, mainly from the stomach, in humans and rodents. It can perform the biological function of... (Review)
Review
Ghrelin, an endogenous brain-gut peptide, is secreted in large quantities, mainly from the stomach, in humans and rodents. It can perform the biological function of activating the growth hormone secretagogue receptor (GHSR). Since its discovery in 1999, ample research has focused on promoting its effects on the human appetite and pleasure-reward eating. Extensive, in-depth studies have shown that ghrelin is widely secreted and distributed in tissues. Its role in neurohumoral regulation, such as metabolic homeostasis, inflammation, cardiovascular regulation, anxiety and depression, and advanced cancer cachexia, has attracted increasing attention. However, the effects and regulatory mechanisms of ghrelin on obesity, gastrointestinal (GI) inflammation, cardiovascular disease, stress regulation, cachexia treatment, and the prognosis of advanced cancer have not been fully summarized. This review summarizes ghrelin's numerous effects in participating in a variety of biochemical pathways and the clinical significance of ghrelin in the regulation of the homeostasis of organisms. In addition, potential mechanisms are also introduced.
Topics: Cachexia; Ghrelin; Humans; Inflammation; Neoplasms; Receptors, Ghrelin
PubMed: 36235843
DOI: 10.3390/nu14194191 -
Endocrine Development 2013Almost all circulating gut peptides contribute to the control of food intake by signalling satiety. One important exception is ghrelin, the only orexigenic peptide... (Review)
Review
Almost all circulating gut peptides contribute to the control of food intake by signalling satiety. One important exception is ghrelin, the only orexigenic peptide hormone thus far described. Ghrelin secretion increases before meals and behavioural and electrophysiological evidence shows that ghrelin acts in the hypothalamus via homeostatic pathways to signal hunger and increase food intake and adiposity. These findings strongly suggest that ghrelin is a dynamically regulated peripheral hunger signal. However, ghrelin also interacts with the brain reward pathways to increase food intake, alter food preference and enhance food reward. Here we discuss ghrelin's role as an endocrine gut-brain reward signal in relation to homeostatic and hedonic feeding control.
Topics: Animals; Brain; Eating; Ghrelin; Humans; Models, Biological; Motivation; Reward; Sex
PubMed: 23652396
DOI: 10.1159/000346058 -
Endocrinology May 2019Much effort has been directed at studying the orexigenic actions of administered ghrelin and the potential effects of the endogenous ghrelin system on food intake, food... (Review)
Review
Much effort has been directed at studying the orexigenic actions of administered ghrelin and the potential effects of the endogenous ghrelin system on food intake, food reward, body weight, adiposity, and energy expenditure. Although endogenous ghrelin's actions on some of these processes remain ambiguous, its glucoregulatory actions have emerged as well-recognized features during extreme metabolic conditions. The blood glucose-raising actions of ghrelin are beneficial during starvation-like conditions, defending against life-threatening falls in blood glucose, but they are seemingly detrimental in obese states and in certain monogenic forms of diabetes, contributing to hyperglycemia. Also of interest, blood glucose negatively regulates ghrelin secretion. This article reviews the literature suggesting the existence of a blood glucose-ghrelin axis and highlights the factors that mediate the glucoregulatory actions of ghrelin, especially during metabolic extremes such as starvation and diabetes.
Topics: Adiposity; Animals; Blood Glucose; Body Weight; Eating; Energy Metabolism; Ghrelin; Humans; Hyperglycemia; Obesity
PubMed: 30874792
DOI: 10.1210/en.2019-00074 -
Cellular and Molecular Life Sciences :... Mar 2022Ghrelin was first identified as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) in 1999, with the function of stimulating the release of growth... (Review)
Review
Ghrelin was first identified as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) in 1999, with the function of stimulating the release of growth hormone (GH), while nesfatin-1 was identified in 2006. Both peptides are secreted by the same kind of endocrine cells, X/A-like cells in the stomach. Compared with ghrelin, nesfatin-1 exerts opposite effects on energy metabolism, glucose metabolism, gastrointestinal functions and regulation of blood pressure, but exerts similar effects on anti-inflammation and neuroprotection. Up to now, nesfatin-1 remains as an orphan ligand because its receptor has not been identified. Several studies have shown the effects of nesfatin-1 are dependent on the receptor of ghrelin. We herein compare the effects of nesfatin-1 and ghrelin in several aspects and explore the possibility of their interactions.
Topics: Animals; Diabetes Mellitus; Ghrelin; Humans; Nucleobindins
PubMed: 35239020
DOI: 10.1007/s00018-022-04193-6