Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation

Hopkins, A. Lynne; Nelson, Timothy A. S.; Guschina, Irina A.; Parsons, Lydia; Lewis, C L; Brown, Richard C. D.; Christian, Helen C.; Davies, J. S.; Wells, Timothy S.

doi:10.1038/srep45541

Cited by 46 publications

(57 citation statements)

References 51 publications

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“…On the other hand, unacylated‐ghrelin does not share the protective effect of acyl‐ghrelin in a mouse model of PD . Intriguingly, the post‐translational acylation of ghrelin by the enzyme, ghrelin‐O‐acyl transferase, may provide a novel mechanism for tissue specific regulation of acyl‐ghrelin levels . In addition, although the role of the obestatin peptide remains unclear, it is distinct from acyl‐ghrelin in certain contexts.…”

Section: Calorie Restriction Regulates Brain Functionmentioning

confidence: 99%

“…113 Intriguingly, the post-translational acylation of ghrelin by the enzyme, ghrelin-O-acyl transferase, 114 may provide a novel mechanism for tissue specific regulation of acyl-ghrelin levels. 115 In addition, although the role of the obestatin peptide remains unclear, it is distinct from acyl-ghrelin in certain contexts. For example, obestatin has an opposing effect on ingestive behaviour 116 and does not modulate GH secretion.…”

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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“…This unique post-translational modification is catalyzed by the enzyme GOAT within the endoplasmic reticulum of ghrelin cells, and occurs before the peptide is processed by prohormone convertase 1/3, stored, and secreted [12, 14, 15]. It also has been claimed that ghrelin can undergo acylation after its secretion, within certain target tissues [16]. Binding of ghrelin to its only known receptor, GHSR, requires this acylation step.…”

Section: Biology Of the Ghrelin Systemmentioning

confidence: 99%

Ghrelin as a Survival Hormone

Mani

Zigman

2017

Trends in Endocrinology & Metabolism

106

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Ghrelin administration induces food intake and body weight gain. Based on these actions, the ghrelin system was initially proposed as an anti-obesity target. Subsequent studies using genetic mouse models have raised doubts about the role of the endogenous ghrelin system in mediating body weight homeostasis or obesity. However, this is not to say that the endogenous ghrelin system is not important metabolically or otherwise. This manuscript reviews an emerging concept in which the endogenous ghrelin system serves an essential function during extreme nutritional and psychological challenges to defend blood glucose, protect body weight, avoid exaggerated depression, and ultimately allow survival.

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“…While this processing pathway for ghrelin maturation and acylation has been well established, a recent study suggests a potential new level of regulation within ghrelin signaling (Hopkins et al, 2017). Hopkins and co-workers demonstrated that both unacylated and acylated ghrelin promote bone marrow adipogenesis in mice in the presence of GOAT, with these effects absent in GOAT knockout mice.…”

Section: Discovery and Characterization Of Ghrelinmentioning

confidence: 99%

The octanoylated energy regulating hormone ghrelin: An expanded view of ghrelin’s biological interactions and avenues for controlling ghrelin signaling

Cleverdon

McGovern-Gooch

Hougland

2016

Molecular Membrane Biology

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Ghrelin is a small peptide hormone that requires a unique post-translational modification, serine octanoylation, to bind and activate the GHS-R1a receptor. Initially demonstrated to stimulate hunger and appetite, ghrelin-dependent signaling is implicated in a variety of neurological and physiological processes influencing diseases such as diabetes, obesity, and Prader-Willi syndrome. In addition to its cognate receptor, recent studies have revealed ghrelin interacts with a range of binding partners within the bloodstream. Defining the scope of ghrelin's interactions within the body, understanding how these interactions work in concert to modulate ghrelin signaling, and developing molecular tools for controlling ghrelin signaling are essential for exploiting ghrelin for therapeutic effect. In this review, we discuss recent findings regarding the biological effects of ghrelin signaling, outline binding partners that control ghrelin trafficking and stability in circulation, and summarize the current landscape of inhibitors targeting ghrelin octanoylation.

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Unacylated ghrelin promotes adipogenesis in rodent bone marrow via ghrelin O-acyl transferase and GHS-R1a activity: evidence for target cell-induced acylation

Cited by 46 publications

References 51 publications

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

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

Ghrelin as a Survival Hormone

The octanoylated energy regulating hormone ghrelin: An expanded view of ghrelin’s biological interactions and avenues for controlling ghrelin signaling

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