Ghrelin as a Survival Hormone

Mani, Bharath K.; Zigman, Jeffrey M.

doi:10.1016/j.tem.2017.10.001

Cited by 106 publications

(103 citation statements)

References 97 publications

(165 reference statements)

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“…Ghrelin has broad metabolic roles (Collden et al, 2017). It is a potent stimulant of growth hormone release, increases fat deposition, and increases circulating glucose levels (Mani and Zigman 2017). …”

Section: Roles Of Gi Hormonesmentioning

confidence: 99%

“…A number of other roles of GI hormones have been identified, for example GLP-2 stimulates gut mucosal growth and repair (Burrin et al 2007), EEC are the source of 5-HT for platelet stores (Mawe and Hoffman 2013) and ghrelin has anti-depressant and anxiolytic effects (Mani and Zigman 2017). Several gut hormones influence the intestinal immune system (Worthington et al 2018).…”

Section: Roles Of Gi Hormonesmentioning

confidence: 99%

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Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme

Fothergill

Furness

2018

Histochem Cell Biol

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Enteroendocrine cells were historically classified by a letter code, each linked to a single hormone, deduced to be the only hormone produced by the cell. One type, the L cell, was recognised to store and secrete two products, peptide YY (PYY) and glucagon-related peptides. Many other exceptions to the one cell – one hormone classifications have been reported over the last 40 years or so, and yet the one hormone dogma has persisted. In the last 6 years, a plethora of data has appeared that makes the concept unviable. Here we describe the evidence that multiple hormone transcripts and their products reside in single cells and evidence that the hormones are often, but not always, processed into separate storage vesicles. It has become clear that most enteroendocrine cells contain multiple hormones. For example, most secretin cells contain 5-hydroxytryptamine (5-HT), and in mouse many of these also contain cholecystokinin (CCK). Furthermore, CCK cells also commonly store ghrelin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), neurotensin, and PYY. Several hormones, for example secretin and 5-HT, are in separate storage vesicles at a subcellular level. Hormone patterns can differ considerably between species. Another complication is that relative levels of expression vary substantially. This means that data are significantly influenced by the sensitivities of detection techniques. For example, a hormone that can be detected in storage vesicles by super-resolution microscopy may not be above threshold for detection by conventional fluorescence microscopy. New nomenclature for cell clusters with common attributes will need to be devised and old classifications abandoned.

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Section: Roles Of Gi Hormonesmentioning

confidence: 99%

Section: Roles Of Gi Hormonesmentioning

confidence: 99%

Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme

Fothergill

Furness

2018

Histochem Cell Biol

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“…Emerging evidence suggests that ghrelin acts as an endogenous survival hormone, increasing levels in circulation as part of the adaptive response to nutritional and other stressors . A 50% caloric restriction (CR) produced hypoglycaemia in Ghrelin −/− and Ghsr −/− mice in the first 16‐20 days; this gradually normalised to levels comparable to CR littermate wild‐type (WT) mice during a 40‐day CR period, whereas a 1‐year‐long chronic 40% CR produced hypoglycaemia in Ghrelin −/− mice but not in Ghsr −/− mice .…”

Section: Introductionmentioning

confidence: 99%

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Bongmba

Lee

et al. 2019

J Neuroendocrinology

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Ghrelin is a gut hormone that signals to the hypothalamus to stimulate growth hormone release, increase food intake and promote fat deposition. The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS‐R), is highly expressed in the brain, with the highest expression in agouti‐related peptide (AgRP) neurones in the hypothalamus. Compelling evidence indicates that ghrelin serves as a survival hormone with respect to maintaining blood glucose and body weight during nutritional deficiencies. Recent studies have demonstrated that AgRP neurones are involved in metabolic and behavioural adaptation to an energy deficit to improve survival. In the present study, we used a neuronal subtype‐specific GHS‐R knockout mouse (AgRP‐Cre;Ghsrf/f) to investigate the role of GHS‐R in hypothalamic AgRP neurones in metabolic and behavioural adaptation to hypocaloric restricted feeding. We subjected the mice to a restricted feeding regimen of 40% mild calorie restriction (CR), with one‐quarter of food allotment given in the beginning of the light cycle and three‐quarters given at the beginning of the dark cycle, to mimic normal mouse intake pattern. The CR‐fed AgRP‐Cre;Ghsrf/f mice exhibited reductions in body weight, fat mass and blood glucose. Metabolic profiling of these CR‐fed AgRP‐Cre;Ghsrf/f mice showed a trend toward reduced basal metabolic rate, significantly reduced core body temperature and a decreased expression of thermogenic genes in brown adipose tissue. This suggests a metabolic reset to a lower threshold. Significantly increased physical activity, a trend toward increased food anticipatory behaviour and altered fuel preferences were also observed in these mice. In addition, these CR‐fed AgRP‐Cre;Ghsrf/f mice exhibited a decreased counter‐regulatory response, showing impaired hepatic glucose production. Lastly, hypothalamic gene expression in AgRP‐Cre;Ghsrf/f mice revealed increased AgRP expression and a decreased expression of genes in β‐oxidation pathways. In summary, our data suggest that GHS‐R in AgRP neurones is a key component of the neurocircuitry involved in metabolic adaptation to calorie restriction.

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“…As the GHSR is expressed in many regions throughout the CNS (Zigman et al, 2006), it is likely that specific feeding behaviours require coordinated action of the GHSR in areas such as the hippocampus and the lateral hypothalamus (Hsu et al, 2015), important for learning, memory, and arousal in the context of food reward. Overall, it seems that GHSR signaling generally serves to enhance the motivational state of the animal to seek, work for and consume palatable foods and this seems consistent with the notion that the ghrelin system exists to support survival of the organism in times of challenge (Mani and Zigman, 2017).…”

Section: Chapter 5: General Discussionsupporting

confidence: 67%

Investigating the Role of the Growth Hormone Secretagogue Receptor in Food-Motivated Behaviours

King¹

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Ghrelin as a Survival Hormone

Cited by 106 publications

References 97 publications

Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme

Diversity of enteroendocrine cells investigated at cellular and subcellular levels: the need for a new classification scheme

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Investigating the Role of the Growth Hormone Secretagogue Receptor in Food-Motivated Behaviours

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