Obestatin promotes proliferation and survival of adult hippocampal progenitors and reduces amyloid-β-induced toxicity

Gargantini, Eleonora; Lazzari, Laura; Settanni, Fabio; Taliano, Marina; Trovato, Letizia; Gesmundo, Iacopo; Ghigo, Ezio; Granata, Riccarda

doi:10.1016/j.mce.2015.11.008

Cited by 22 publications

(24 citation statements)

References 59 publications

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“…For example, obestatin has an opposing effect on ingestive behaviour and does not modulate GH secretion . However, both peptides have beneficial effects on memory and reduce toxicity to AB . Given that obestatin does not cross the BBB, its central mechanism of action is likely to be distinct from that of acyl‐ghrelin.…”

Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 99%

“…117 However, both peptides have beneficial effects on memory 118,119 and reduce toxicity to AB. 120 Given that obestatin does not cross the BBB, 121 its central mechanism F I G U R E 3 Schematic of putative cell-extrinsic mechanisms of acyl-ghrelin-mediated adult hippocampal neurogenesis (AHN). Because ghrelin-receptor, growth hormone secretagogue receptor (GHSR), is expressed in mature granule neurones of the dentate gyrus (DG) but not in neural stem/progenitor cells (NSPCs), we suggest acyl-ghrelin-mediated AHN is supported by: (1) of action is likely to be distinct from that of acyl-ghrelin.…”

Section: -Methyl-4-isoxazolepropionic Acid (Ampa) Receptors On Excitmentioning

confidence: 99%

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Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

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Calorie intake is essential for regulating normal physiological processes and is fundamental to maintaining life. Indeed, both extremes of calorie intake result in increased morbidity and mortality. In this review, we discuss the effect of calorie intake on adult brain function, with an emphasis on the beneficial effects of mild calorie restriction.Recent findings relating to the regenerative and protective effects of the gastrointestinal hormone, ghrelin, suggest that it may underlie the beneficial effects of calorie restriction. We discuss the putative cellular mechanisms underlying the action of ghrelin and their possible role in supporting healthy brain ageing. K E Y W O R D Sacyl-ghrelin, adult hippocampal neurogenesis, calorie restriction, diet-induced obesity | INTRODUCTIONThe energy status of an organism is tightly controlled around a setpoint by hormonal and neural systems. These neuroendocrine checks and balances promote homeostasis, thereby ensuring an appropriate energy supply for the energetic demands of metabolism, physical activity, growth and repair.Disturbances to this homeostasis result in multiple physiological impairments, including age-related conditions such as type 2 dibetes mellitus and obesity. Perhaps less well recognised are the consequences of metabolic dysfunction on neuronal health and cognition.Diet-induced obesity (DIO) is a risk factor for neurodegenerative diseases such as Parkinson's disease (PD) and dementia. Conversely, calorie restriction (CR) (ie, an approximate 30% reduction in calorie intake) protects against neurodegeneration and promotes cognitive function (Figure 1). Indeed, there is a growing body of work supporting the CR paradigm as a tool for promoting lifespan and, perhaps more importantly, healthspan.1 However, the physiological mechanisms underlying these effects are not fully understood. Here, we review literature that identifies calorie intake as an important regulator of nerve cell function, with important implications for neurodegenerative disorders. Moreover, we describe recent research showing that CR promotes new neurone formation (neurogenesis) and neuroprotection in the adult brain and discuss the possible mechanisms that underpin this effect. | CALORIE RESTRICTION REGULATES BRAIN FUNCTIONCalorie restriction, in the absence of malnutrition, has beneficial effects on brain function, including reducing the incidence of age-related neurodegenerative disease, 2 eliciting anti-depressant behaviour 3 and improving memory function in rodents. 4 In nonhuman primates, prolonged CR in adulthood decreases the incidence of age-related disease, including measures of brain atrophy and glucose regulation. 5-7Translation of the carefully controlled CR experiments from preclinical models to humans is problematic. In particular, it is difficult to re-capitulate experimental controls such as genetic background and home environment (diet, temperature and lighting) that are standard in biomedical laboratory research. Nonetheless, in adult humans, a 3-month period of CR impr...

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Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 99%

Section: -Methyl-4-isoxazolepropionic Acid (Ampa) Receptors On Excitmentioning

confidence: 99%

Less is more: Caloric regulation of neurogenesis and adult brain function

Morgan

Andrews

Davies

2017

J Neuroendocrinology

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“…Our present findings have demonstrated that the selective antagonist of ghrelin receptor (D‐Lys3)‐GHRP‐6 did not alter the antiadrenergic action of obestatin, suggesting GHS‐R1a‐independent effect of the peptide and involvement of a different receptor. Interestingly, we have previously shown that the glucagon‐like peptide 1 receptor (GLP‐1R) may be implicated in the physiopathological actions of obestatin in several cell types 29, 49, 51, 52. This may also be possible for cardiomyocytes and endothelial cells, which express GLP‐1R 53, although more studies are needed to clarify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway

Penna

Tullio

Femminò

et al. 2017

J Cellular Molecular Medi

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Patients with ischaemic heart disease or chronic heart failure show altered levels of obestatin, suggesting a role for this peptide in human heart function. We have previously demonstrated that GH secretagogues and the ghrelin gene‐derived peptides, including obestatin, exert cardiovascular effects by modulating cardiac inotropism and vascular tone, and reducing cell death and contractile dysfunction in hearts subjected to ischaemia/reperfusion (I/R), through the Akt/nitric oxide (NO) pathway. However, the mechanisms underlying the cardiac actions of obestatin remain largely unknown. Thus, we suggested that obestatin‐induced activation of PI3K/Akt/NO and PKG signalling is implicated in protection of the myocardium when challenged by adrenergic, endothelinergic or I/R stress. We show that obestatin exerts an inhibitory tone on the performance of rat papillary muscle in both basal conditions and under β‐adrenergic overstimulation, through endothelial‐dependent NO/cGMP/PKG signalling. This pathway was also involved in the vasodilator effect of the peptide, used both alone and under stress induced by endothelin‐1. Moreover, when infused during early reperfusion, obestatin reduced infarct size in isolated I/R rat hearts, through an NO/PKG pathway, comprising ROS/PKC signalling, and converging on mitochondrial ATP‐sensitive potassium [mitoK(ATP)] channels. Overall, our results suggest that obestatin regulates cardiovascular function in stress conditions and induces cardioprotection by mechanisms dependent on activation of an NO/soluble guanylate cyclase (sGC)/PKG pathway. In fact, obestatin counteracts exaggerated β‐adrenergic and endothelin‐1 activity, relevant factors in heart failure, suggesting multiple positive effects of the peptide, including the lowering of cardiac afterload, thus representing a potential candidate in pharmacological post‐conditioning.

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“…Obestatin has also shown to enhance the proliferation of adult hippocampal progenitor cells (AHPs) in vitro. Rat AHPs treated with various concentrations of obestatin (1, 10, 100 and 500nM) all showed a significant increase in cell proliferation and survival, and also a reduction in caspase 3 activity indicating anti-apoptotic effects also (Gargantini et al, 2016).…”

Section: Ghrelin Treatment Has Been Shown To Induce the Expression Ofmentioning

confidence: 98%

Ghrelin-axis function in the context of Adult Hippocampal Neurogenesis

Hornsby¹

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Obestatin promotes proliferation and survival of adult hippocampal progenitors and reduces amyloid-β-induced toxicity

Cited by 22 publications

References 59 publications

Less is more: Caloric regulation of neurogenesis and adult brain function

Less is more: Caloric regulation of neurogenesis and adult brain function

Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway

Ghrelin-axis function in the context of Adult Hippocampal Neurogenesis

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