Expression of the growth hormone secretagogue receptor 1a (GHS‐R1a) in the brain

Айрапетов, М. И.; Ереско, С. О.; Лебедев, А. А.; Bychkov, Eugenii R.; Shabanov, Petr D.

doi:10.14814/phy2.15113

Cited by 14 publications

(6 citation statements)

References 48 publications

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“…As a ghrelin and LEAP2 receptor, GHSR is widely distributed in the hypothalamus ( 53 ). In addition to neuropeptides, we examined the expression of GHSR.…”

Section: Discussionmentioning

confidence: 99%

Involvement of POMC neurons in LEAP2 regulation of food intake and body weight

Chu

Peng

et al. 2022

Front. Endocrinol.

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Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.

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“…As a ghrelin and LEAP2 receptor, GHSR is widely distributed in the hypothalamus ( 53 ). In addition to neuropeptides, we examined the expression of GHSR.…”

Section: Discussionmentioning

confidence: 99%

Involvement of POMC neurons in LEAP2 regulation of food intake and body weight

Chu

Peng

et al. 2022

Front. Endocrinol.

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“…Acyl-ghrelin, a major form of ghrelin, has been shown to exert neuroprotective effects against PD by binding to GHS-R1a, which is expressed in the striatum and SNpc. 73,74 It has been found to inhibit apoptosis by enhancing mitophagy and mitochondria biogenesis. 28 A study using caloric-restricted ghrelin KO or ghrelin WT mice has indicated AMPK as a target protein to maintain energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Teaghrelin protected dopaminergic neurons in MPTP‐induced Parkinson's disease animal model by promoting PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC1‐α‐mediated mitochondrial biogenesis

Jhuo,

Chen,

Tzen

et al. 2024

Environmental Toxicology

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Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD. Mitochondrial dysfunction, a common cellular hallmark in both familial and sporadic forms of Parkinson's disease (PD), is assumed to play a significant role in pathologic development and progression of the disease. Teaghrelin, a unique bioactive compound in some oolong tea varieties, has been demonstrated to protect SH‐SY5Y cells against 1‐methyl‐4‐phenylpyridinium induced neurotoxicity by binding to the ghrelin receptor to activate the AMPK/SIRT1/PGC‐1α pathway. In this study, an animal model was established using a neurotoxin, 1‐methyl‐4phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a byproduct of a prohibited drug, to evaluate the oral efficacy of teaghrelin on PD by monitoring motor dysfunction of mice in open field, pole, and bean walking tests. The results showed that MPTP‐induced motor dysfunction of mice was significantly attenuated by teaghrelin supplementation. Tyrosine hydroxylase and dopamine transporter protein were found reduced in the striatum and midbrain of MPTP‐treated mice, and significantly mitigated by teaghrelin supplementation. Furthermore, teaghrelin administration enhanced mitophagy and mitochondria biogenesis, which maintained cell homeostasis and prevented the accumulation of αSyn and apoptosis‐related proteins. It seemed that teaghrelin protected dopaminergic neurons in MPTP‐treated mice by increasing PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC‐1α‐mediated mitochondria biogenesis, highlighting its potential therapeutic role in maintaining dopaminergic neurons function in PD.

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“…Ghrelin is primarily secreted by oxyntic cells of the gastric mucosa, and its action is due to acylation process that allows its binding to growth hormone secretagogue receptor (GHSR), highly expressed in ARC ( 104 – 106 ). However, it is important to note that GHSR is differently expressed in ARC neuronal populations: about 90% of NPY/AgRP expressed GHSR compared to ~10% POMC neurons ( 107 , 108 ). Consequently, ghrelin mainly activates NPY/AgRP neurons promoting food intake ( 109 ).…”

Section: The Circadian System: An Orchestra Of Signals Synchronizes F...mentioning

confidence: 99%

Chrono-communication and cardiometabolic health: The intrinsic relationship and therapeutic nutritional promises

Senesi

Ferrulli²,

Luzi³

et al. 2022

Front. Endocrinol.

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Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

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Expression of the growth hormone secretagogue receptor 1a (GHS‐R1a) in the brain

Cited by 14 publications

References 48 publications

Involvement of POMC neurons in LEAP2 regulation of food intake and body weight

Involvement of POMC neurons in LEAP2 regulation of food intake and body weight

Teaghrelin protected dopaminergic neurons in MPTP‐induced Parkinson's disease animal model by promoting PINK1/Parkin‐mediated mitophagy and AMPK/SIRT1/PGC1‐α‐mediated mitochondrial biogenesis

Chrono-communication and cardiometabolic health: The intrinsic relationship and therapeutic nutritional promises

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