Two ghrelin receptor agonists for adults with malnutrition: a systematic review and meta-analysis

Su, Jianhua; Bao, Jisheng; Tang, Yin; Liu, Menglan; Yu, Haibin; Han, Yi; Huang, Wei; Zhou, Suming

doi:10.1186/s12937-016-0214-5

Cited by 11 publications

(9 citation statements)

References 61 publications

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“…Which role the ghrelin receptor may play in the absence of its only confirmed ligand, ghrelin (reviewed by Kaiya et al [ 38 ]), is also unknown. Cancer research has demonstrated alternative non-peptide ligands can bind to ghrelin receptors [ 39 , 40 ], thus as yet unknown non-ghrelin compounds could potentially be ligands of ghrelin receptors in fish lacking ghrelin.…”

Section: Discussionmentioning

confidence: 99%

Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish

et al. 2018

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BackgroundThe ballan wrasse (Labrus bergylta) belongs to a large teleost family containing more than 600 species showing several unique evolutionary traits such as lack of stomach and hermaphroditism. Agastric fish are found throughout the teleost phylogeny, in quite diverse and unrelated lineages, indicating stomach loss has occurred independently multiple times in the course of evolution. By assembling the ballan wrasse genome and transcriptome we aimed to determine the genetic basis for its digestive system function and appetite regulation. Among other, this knowledge will aid the formulation of aquaculture diets that meet the nutritional needs of agastric species.ResultsLong and short read sequencing technologies were combined to generate a ballan wrasse genome of 805 Mbp. Analysis of the genome and transcriptome assemblies confirmed the absence of genes that code for proteins involved in gastric function. The gene coding for the appetite stimulating protein ghrelin was also absent in wrasse. Gene synteny mapping identified several appetite-controlling genes and their paralogs previously undescribed in fish. Transcriptome profiling along the length of the intestine found a declining expression gradient from the anterior to the posterior, and a distinct expression profile in the hind gut.ConclusionsWe showed gene loss has occurred for all known genes related to stomach function in the ballan wrasse, while the remaining functions of the digestive tract appear intact. The results also show appetite control in ballan wrasse has undergone substantial changes. The loss of ghrelin suggests that other genes, such as motilin, may play a ghrelin like role. The wrasse genome offers novel insight in to the evolutionary traits of this large family. As the stomach plays a major role in protein digestion, the lack of genes related to stomach digestion in wrasse suggests it requires formulated diets with higher levels of readily digestible protein than those for gastric species.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4570-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish

et al. 2018

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“…However, the action of GHSR-1a signalling on reward areas is closely intertwined with homeostasis, and is regulated in this respect [ 188 , 384 ]. The peripheral metabolic confounders in systemic ghrelin therapy, particularly relating to glucose homeostasis, may be contributing to the lack of successful preclinical moieties translating to clinical practice [ 387 ]. BBB-penetrant ghrelin agonists should bypass the homeostatic “gating” at the level of the arcuate nucleus and NTS.…”

Section: Discussionmentioning

confidence: 99%

From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation

Howick

Griffin

Cryan

et al. 2017

IJMS

126

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Ghrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging. This is due to many factors, ranging from the complexity of the ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR-1a) internalisation and heterodimerization, to biased ligand interactions and compensatory neuroendocrine outputs. Not least is the ubiquitous expression of the GHSR-1a, which makes it impossible to modulate centrally-mediated appetite regulation without encroaching on the various peripheral functions attributable to ghrelin. It is becoming clear that ghrelin’s central signalling is critical for its effects on appetite, body weight regulation and incentive salience of food. Improving the ability of ghrelin ligands to penetrate the blood brain barrier would enhance central delivery to GHSR-1a expressing brain regions, particularly within the mesolimbic reward circuitry.

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“…The therapeutic roles of exogenous GHS-R1a agonists in disorders, such as malnutrition, growth hormone deficiency, gastrointestinal hypomotility, and protein-energy wasting, are well known [ 53 , 54 , 55 , 56 ]. Despite the finding that a ghrelin agonist improved cognitive function in AD patients and animal models, the specific effects on Aβ accumulation varied [ 47 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

Jeong

Shin

Park

et al. 2018

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor. Interestingly, previous studies have shown that ghrelin improves cognitive impairments and attenuates neuronal death and neuroinflammation in several neurological disorders. However, it is unknown whether MK-0677 can affect Aβ accumulation or Aβ-mediated pathology in the brains of patients with AD. Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD. MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice. To visualize Aβ accumulation, neuroinflammation, and neurodegeneration, thioflavin-S staining and immunostaining with antibodies against Aβ (4G8), ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and synaptophysin were conducted in the neocortex of 5XFAD and wild-type mice, and to evaluate changes of phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) levels, immunostaining with antibody against pCREB was performed in dentate gyrus of the hippocampus of 5XFAD and wild-type mice. The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice. Our results showed that activation of the ghrelin receptor with MK-0677 inhibited the Aβ burden, neuroinflammation, and neurodegeneration, which suggested that MK-0677 might have potential as a treatment of the early phase of AD.

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Two ghrelin receptor agonists for adults with malnutrition: a systematic review and meta-analysis

Cited by 11 publications

References 61 publications

Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish

Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish

From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation

MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

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