Ghrelin receptor controls obesity by fat burning

Sun, Yuxiang

doi:10.18632/oncotarget.3668

Cited by 9 publications

(7 citation statements)

References 8 publications

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“…Ghrelin receptor GHS-R is an important regulator of thermogenesis. 57 The ablation of this receptor increases energy expenditure by increasing thermogenesis in brown adipose tissue (by uncoupling oxidative phosphorylation from electron transport chain due to increased UCP1expression), 52,94 which is independent of food intake or physical activity. 57 This finding has significant practical implications since it has been proposed that GHS-R antagonists may represent a new therapeutic class effective in obesity 94 and not requiring restrictive diets or physical activity.…”

Section: Ghrelin and Energy Expenditurementioning

confidence: 99%

“…In conclusion, circulating ghrelin level in humans are low under conditions of positive energy balance, Table 1. The main effects of ghrelin that can influence energy metabolism Food intake 1,35 ↑ appetite/↑ food intake ↑ hedonic aspect of eating ↑ motivation to obtain food ↑ food seeking behaviours Gastrointestinal function [47][48][49][50] ↑ gastric motility ↑ gastric acid secretion and digestive enzymes Adipose tissue 26,39,53,58 ↑ lipogenesis ↑ adipogenesis (↑ differentiation and proliferation of preadipocytes) ↓ lipid oxidation Intermediary metabolisms 57,62,79,82,90,92,93 ↓ insulin secretion ↑ hepatic gluconeogenesis ↓ insulin sensitivity ↑ glucagon secretion ↑ hepatic lipogenesis GLP-1 secretagogue Energy expenditure 52,57,94,95 ↓ energy expenditure ↓ thermogenesis in BAT ↓ sympathetic nervous system in BAT either in acute conditions (food intake) or chronic conditions (obesity). Elevated circulating ghrelin levels are found in fasting conditions and in patients with anorexia of various causes.…”

Section: Ghrelin and Energy Expenditurementioning

confidence: 99%

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Effects of ghrelin in energy balance and body weight homeostasis

Mihalache¹,

Gherasim²,

Niţă³

et al. 2016

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ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, ghsR1a, was also identified. ghrelin, the endogenous ligand for the gh secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O-acyltransferase enzyme (gOAT). The literature even mentions an extremely complex ghrelin/gOAT/ghsR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers

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Section: Ghrelin and Energy Expenditurementioning

confidence: 99%

Section: Ghrelin and Energy Expenditurementioning

confidence: 99%

Effects of ghrelin in energy balance and body weight homeostasis

Mihalache¹,

Gherasim²,

Niţă³

et al. 2016

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“…In all, there were very few serious cardiovascular TEAEs and comparatively few overall cardiovascular TEAEs, with a small number of findings of QTc prolongation on ECG. However, there is a need for careful assessment of cardiovascular risks given inconclusive findings from experimental studies 49‐53 . Ghrelin acting through the growth hormone secretagogue receptor may regulate energy homeostasis by burning fat to generate heat 49 .…”

Section: Discussionmentioning

confidence: 99%

“…However, there is a need for careful assessment of cardiovascular risks given inconclusive findings from experimental studies 49‐53 . Ghrelin acting through the growth hormone secretagogue receptor may regulate energy homeostasis by burning fat to generate heat 49 . Peripheral tissue effects of ghrelin on interstitial levels of glucose, glycerol and lactate have been reported, concluding that ghrelin increased insulin sensitivity 50 .…”

Section: Discussionmentioning

confidence: 99%

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Camilleri

Lembo

McCallum

et al. 2020

Aliment Pharmacol Ther

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Background: Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials. Aim:To assess the safety and tolerability of relamorelin across phase 2 trials. Methods: Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1-and 2-week, singleblind placebo run-ins.Results: Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively). Conclusions:Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.

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“…Higher levels of ghrelin are associated with low levels of resting metabolic rate (RMR) and postprandial thermogenesis (261). The ablation of GHS-R increases energy expenditure by increasing thermogenesis in BAT through increasing uncoupling oxidative phosphorylation, which is independent of food intake or physical activity (262). Ghrelin suppresses energy expenditure and thermogenesis in BAT via its inhibitory effect on BAT sympathetic nerve activity (263) (Figure 1.6).…”

Section: Effects Of Ghrelin On Food Intake and Energy Metabolismmentioning

confidence: 99%

Evaluation of Pharmacological Modification of Growth Hormone Secretagogue Receptor in a Mouse Model of Non-Obese Type 2 Diabetes Mellitus

Mosa¹,

Mofeed²

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While it appears that obesity is associated with the higher incidence of type 2 diabetes mellitus (T2DM), recent findings that T2DM affects non-obese people are becoming more noticeable. Many of those who are not obese by traditional weight measurements have an increased percentage of body fat distributed predominately in the abdominal and visceral regions. Disorders of lipid metabolism play a major role in the pathogenesis of this nonobese diabetic phenotype. For examples, lipodystrophic patients develop insulin resistance due to insufficient adipose tissue and aged lean people with diabetes have defects in mitochondrial lipid oxidative mechanisms. Such non-obese diabetic patients are at increased risk of developing cardiovascular (CVD) complications. The management of non-obese T2DM should focus not only on life style modifications or blood glucose control but also strategies for correction of lipid metabolic aberrations. Growth hormone (GH) exerts powerful influences on growth and body composition. In obese animal models and human, GH is known to correlate inversely with insulin concentrations. Some studies suggest that insulin may have a direct inhibitory effect on GH secretion, whereas others showed that insulin inhibits GH secretion via suppression of growth hormone releasing hormone (GHRH) or stimulation of somatostatin (SST). Although GH-insulin relationship is well documented in obesity, studies of this GH-insulin relationship in non-obese diabetes are sparse and contradictory. Thus, this study aimed to investigate the pulsatile GH profile and its regulatory factors in MKR mice which are non-obese diabetic mice generated by igf-1 receptor mutation in skeletal muscle. Our observations demonstrated that unlike obese mice, MKR mice had normal to higher pulsatile GH secretion at different age groups. Nevertheless, there were no detectable changes in gene expressions of hypothalamic GHRH and SST. Interestingly, hypothalamic orexigenic NPY gene expression was increased that might affect GH secretion. These findings suggest that the relationship between GH and insulin was altered in MKR mice, leading to higher GH concentrations despite hyperinsulinaemia. Given that MKR mice exhibited postnatal growth retardation, we anticipated that endogenous GH levels would increase to facilitate rapid linear growth and promote muscle development that assist nutrient uptake and utilization.Therapy using growth hormone secretagogues (GHS) that increase endogenous GH secretion through binding to the ghrelin receptor (GHS-R1a) might have beneficial effects on lipid metabolism with less adverse effects on glucose metabolism than exogenous GH administration. Recent studies have provided some interesting avenues for further exploration on how Hexarelin, one of synthetic peptide GHS, enhanced fat metabolism of white adipose tissue (WAT) via CD36 activation independently of GHS-R1a. To address the effects of Hexarelin in non-obese diabetes, MKR were received daily intraperitoneal (I.P.) injection of Hexarelin (200ug/kg body ...

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Ghrelin receptor controls obesity by fat burning

Cited by 9 publications

References 8 publications

Effects of ghrelin in energy balance and body weight homeostasis

Effects of ghrelin in energy balance and body weight homeostasis

Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data

Evaluation of Pharmacological Modification of Growth Hormone Secretagogue Receptor in a Mouse Model of Non-Obese Type 2 Diabetes Mellitus

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