Ghrelin Induces Abdominal Obesity via GHS-R-Dependent Lipid Retention

Davies, Jane; Kotokorpi, Pia; Eccles, Sinan R.; Barnes, Sarah K.; Tokarczuk, Pawel; Allen, Stuart M.; Whitworth, Hilary; Guschina, Irina A.; Evans, Bronwen Alice James; Mode, Agneta; Zigman, Jeffrey M.; Wells, Timothy N.C.

doi:10.1210/jcem.94.5.9994

Cited by 24 publications

(48 citation statements)

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“…Some studies showed a direct role for ghrelin in enhancing insulinstimulated glucose uptake in isolated epididymal white adipose tissue [48] and adipogenesis [49], but others showed the opposite, such as increased lipolysis [41,47]. These contradictory results may arise from the use of different modes of ghrelin exposure and analysis of adipocytes from different locations, consistent with reports that show fat-depot specific sensitivity to ghrelin [44]. A recent study by Vestergaard et al sought to study direct effects of ghrelin on skeletal muscle substrate metabolism and insulin sensitivity in human subjects [50].…”

Section: The Effect Of Ghrelin In Other Periph-eral Tissuessupporting

confidence: 74%

“…In vivo studies indicate ghrelin regulates adipogenesis both directly and indirectly via central mechanisms [43]. The GHSR is expressed in white adipose tissue [44][45][46] and ghrelin treatment increases the size of adipocytes, increases the triglyceride concentration and increases UCP2 mRNA expression in this tissue [47]. Central ghrelin also increases enzymes involved with fat storage such as lipoprotein lipase (LPL), acetyl CoA carboxylase (ACC)-, stearoyl CoA desaturase-1 (SCD1) and decreases the rate-limiting enzyme in fat oxidation, CPT1 [43].…”

Section: The Effect Of Ghrelin In Other Periph-eral Tissuesmentioning

confidence: 99%

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A Recent Update on the Role of Ghrelin in Glucose Homeostasis

Briggs

Andrews

2011

CDR

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Recent evidence highlights an important role of ghrelin in glucose homeostasis. In this review we provide a detailed summary of recent advances in this field. We describe the effects of ghrelin on all aspects of glucose homeostasis including glucose-stimulated insulin secretion, hepatic glucose production and insulin stimulated glucose disposal in the peripheral tissues. The existing evidence suggests ghrelin primarily inhibits insulin release from the pancreas and we highlight an important mechanism involving AMPK-UCP2 ATP-stimulated potassium channels and intracellular calcium regulation. Ghrelin increases hepatic glucose production and prevents glucose disposal in muscle and adipose tissues, which collectively leads to hyperglycemia and impaired glucose tolerance. We discuss the important role ghrelin plays in glucose homeostasis during different metabolic states. During severe calorie restriction, ghrelin increases blood glucose concentrations in order to maintain glucose homeostasis. In diet-induced obesity, ghrelin exacerbates hyperglycemia and promotes a diabetic phenotype.

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Section: The Effect Of Ghrelin In Other Periph-eral Tissuessupporting

confidence: 74%

Section: The Effect Of Ghrelin In Other Periph-eral Tissuesmentioning

confidence: 99%

A Recent Update on the Role of Ghrelin in Glucose Homeostasis

Briggs

Andrews

2011

CDR

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“…Although the mechanisms responsible are far from being understood, in vitro studies demonstrate that ghrelin stimulates the differentiation of rat preadipocytes, antagonizes isoproterenol-induced lipolysis (10) and stimulates lipid accumulation as well as TNF␣-induced apoptosis in human visceral adipocytes (11,12). In addition to its direct actions on white adipose tissue (WAT), chronic systemic infusion of ghrelin induces hepatic steatosis, increasing lipid droplet number and triacylglycerol content by a growth-hormone-secretagogue-receptor-1a (GHS-R1a)-dependent mechanism (13). Similarly, chronic central infusion of ghrelin also favors hepatic lipid storage and reduces lipid mobilization (5).…”

mentioning

confidence: 99%

Ghrelin Requires p53 to Stimulate Lipid Storage in Fat and Liver

Porteiro

Díaz‐Ruiz

Martínez³

et al. 2013

Endocrinology

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Ghrelin, a stomach-derived peptide, stimulates feeding behavior and adiposity. For its orexigenic action, ghrelin triggers a central SIRT1/p53/AMPK pathway. The tumor suppressor p53 also plays an important role in white adipose tissue (WAT), where it is up-regulated in the adipocytes of obese mice. It is not known, however, whether p53 has any role in mediating the peripheral action of ghrelin. In the present study, chronic peripheral ghrelin treatment resulted in increased body weight and fat-mass gain in wild-type mice. Correspondingly, mRNA levels of several adipogenic and fat-storage-promoting enzymes were up-regulated in WAT, whereas hepatic triglyceride content and lipogenic enzymes were also increased in wild-type mice following ghrelin treatment. In contrast, mice lacking p53 failed to respond to ghrelin treatment, with their body weight, fat mass, and adipocyte and hepatic metabolism remaining unchanged. Thus, our results show that p53 is necessary for the actions of ghrelin on WAT and liver, leading to changes in expression levels of lipogenic and adipogenic genes, and modifying body weight.

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“…Similarly, GHS-R1a is expressed in adipocytes and in rodent and human adipose tissue [10,22,24,[64][65][66][67][68][69][70], although opposite findings have also been shown [8,47,71]. AG and UAG also bind to common receptor(s) in adipocytes, suggesting the existence of a yet unknown receptor, likely different from GHS-R1a [47].…”

Section: Ghrelin Gene-derived Peptides and Adipocytesmentioning

confidence: 95%

“…AG and UAG either stimulate or have no effect on glucose uptake in 3T3-L1 adipocytes [9,22,65,67]. AG and UAG have been also found to increase fatty acid uptake in 3T3-L1 adipocyte, and AG infusion promoted hepatic steatosis in rats via a GHS-R1a-dependent mechanism [68].…”

Section: Ghrelin Gene-derived Peptides and Adipocytesmentioning

confidence: 99%

Products of the Ghrelin Gene, the Pancreatic β-Cell and the Adipocyte

Granata¹,

Ghigo²

2013

The Ghrelin System

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The ghrelin system comprises acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin, besides the receptor for AG, the growth hormone (GH) secretagogue receptor type 1a (GHS-R1a), and the enzyme-promoting ghrelin acylation, ghrelin O-acyltransferase (GOAT). The ghrelin peptides exert a variety of biological actions, including regulation of energy homeostasis and glucose metabolism, as well as survival and proliferative effects in different cell types. Besides the stomach, its main site of production, ghrelin is expressed in pancreatic islets, where it represents an independent islet cell population. AG exerts insulinostatic actions, UAG has been shown to oppose the AG inhibitory effects on insulin secretion, and obestatin has demonstrated insulinotropic activities. Although differences exist in the regulation of glucose homeostasis, all peptides display survival and antiapoptotic actions in pancreatic β-cells, preserving β-cell mass and function both in vitro and in vivo. The ghrelin system is also expressed in adipose tissue, and ghrelin effects have been demonstrated in both white and brown adipocytes. Indeed, AG, UAG and obestatin promote adipogenesis and glucose uptake, and inhibit adipocyte lipolysis. Interestingly, despite similar effects at the cellular level, results from ghrelin, GHS-R and GOAT knockout mice have indicated that AG display diabetogenic effects in vivo. Conversely, UAG and obestatin positively regulate glucose metabolism, and a new role has been recently proposed for obestatin on adipocyte function and insulin sensitivity.

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Ghrelin Induces Abdominal Obesity via GHS-R-Dependent Lipid Retention

Cited by 24 publications

References 0 publications

A Recent Update on the Role of Ghrelin in Glucose Homeostasis

A Recent Update on the Role of Ghrelin in Glucose Homeostasis

Ghrelin Requires p53 to Stimulate Lipid Storage in Fat and Liver

Products of the Ghrelin Gene, the Pancreatic β-Cell and the Adipocyte

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