Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice

Ma, Xiaoli; Lin, Yuezhen; Lin, Ligen; Qin, Guijun; Pereira, Fred A.; Haymond, Morey W.; Butte, Nancy F.; Sun, Yuxiang

doi:10.1152/ajpendo.00576.2011

Cited by 39 publications

(31 citation statements)

References 61 publications

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“…Ghrelin signaling has increasingly been recognized as a key regulator of obesity, insulin resistance and diabetes; intriguingly, many of these regulatory functions appear to be independent of ghrelin's effect on food intake (4–8). This current review is focused on the most recent findings of ghrelin in glucose homeostasis (9–11), energy-homeostasis (7, 12), heart disease (13–16), muscular atrophy (17, 18), bone metabolism (8, 19, 20), and cancer development/progression (21, 22). …”

Section: Introductionmentioning

confidence: 99%

Ghrelin

Pradhan¹,

Samson²,

Sun³

2013

Current Opinion in Clinical Nutrition and Metabolic Care

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224

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Purpose of review Ghrelin is a multifaceted gut hormone which activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on food intake, fat deposition and growth hormone release. Ghrelin is famously known as the “hunger hormone”. However, ample literature indicates that the functions of ghrelin go well beyond its role as an orexigenic signal. Here we have reviewed some of the most recent findings on ghrelin and its signaling in animals and humans. Recent findings Ghrelin regulates glucose hemostasis by inhibiting insulin secretion and regulating gluconeogenesis/glycogenolysis. Ghrelin signaling decreases thermogenesis to regulate energy expenditure. Ghrelin improves the survival prognosis of myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates bone formation and metabolism by modulating proliferation and differentiation of osteoblasts. Ghrelin is also involved in cancer development and metastasis; ghrelin and GHS-R mRNA are highly expressed in metastatic forms of cancers. Summary In addition to ghrelin's effects on appetite and adiposity, ghrelin signaling also plays crucial roles in glucose- and energy-homeostasis, cardioprotection, muscle atrophy, bone metabolism and cancer. These multifaceted roles of ghrelin make ghrelin and GHS-R highly attractive targets for drug development.

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Section: Introductionmentioning

confidence: 99%

Ghrelin

Pradhan¹,

Samson²,

Sun³

2013

Current Opinion in Clinical Nutrition and Metabolic Care

Self Cite

224

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“…The regulation and interactions between these hormones have previously been described in humans (Klok et al, 2007) and other species (Ma et al, 2012). Most studies on the relationship between food intake-regulating hormones and diet have focused on understanding the underlying mechanisms involved in obesity and its related disorders in humans (Schwarz et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Addition of crude glycerin to pig diets: sow and litter performance, and metabolic and feed intake regulating hormones

Hernández

Orengo

Villodre

2016

Animal

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The continued growth in biofuel production has led to a search for alternative value-added applications of its main by-product, crude glycerin. The surplus glycerin production and a higher cost of feedstuffs have increased the emphasis on evaluating its nutritive value for animal feeding. The aim of this research was to evaluate the effect of the dietary addition of crude glycerin on sow and litter performance, and to determine the serum concentrations of hormones related to energy metabolism and feed intake in sows during gestation and lactation. A total of 63 sows were assigned randomly to one of three dietary treatments, containing 0, 3 or 6% crude glycerin (G0, G3 and G6, respectively) added to a barley-soybean meal-based diet. During gestation, none of the dietary treatments had an effect on performance, while during lactation, glycerin-fed sows consumed less feed than those fed the control diet (3.8 v. 4.2 kg DM/day; P = 0.007). Although lactating sows fed the G3 diet had a higher BW loss than those fed the control diet (−20.6 v. −8.7 kg; P = 0.002), this difference was not reflected in litter performance. In gestation, the inclusion of glycerin did not affect blood concentrations of insulin or cortisol. However, pregnant sows fed diets supplemented with glycerin showed lower concentrations of acyl-ghrelin and higher concentrations of leptin (−55 and +68%, respectively; P < 0.001). In lactating sows, there were no differences between dietary treatments for any of the hormones measured. Pre-prandial acyl-ghrelin concentrations were positively correlated with cortisol concentrations during gestation ( r = 0.81; P = 0.001) and lactation ( r = 0.61; P = 0.015). In conclusion, the inclusion of up to 6% crude glycerin did not affect the performance of sows during the gestation period; however it had a negative effect on the feed intake and weight loss of lactating sows. Moreover, further research is needed to elucidate the potential relationship between glycerin inclusion levels in the diet and the serum concentrations of hormones related to feed intake and energy balance control.Keywords: crude glycerin, feed intake, metabolic hormones, sow ImplicationsAccording to our results, crude glycerin up to 6% could be added to the diet from confirmation of pregnancy without affecting the performance of pregnant sows. Our results also suggest a relationship between the inclusion of glycerin in the diet and the serum concentrations of feed intake regulating hormones, such as acyl ghrelin and leptin; but more studies are needed to increase the understanding of interactions between diet composition and hormone concentration.

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“…The discrepancies of ghrelin effects in different studies may be due to the following reasons: (1) the implications of ghrelin on insulin secretion and glucose metabolism could be different in different energy states like fasting, fed, obese, and diabetic, (2) Ghrelin, GHS-R, and GOAT are all expressed in pancreatic islets, suggesting a role for locally expressed ghrelin that could be different from that of the systemic ghrelin in the regulation of insulin release, (3) some of effects of ghrelin are independent of GHS-R1a and this highlight the complexity of the ghrelinsignaling pathway. This can be indicated by the paradoxical effects of ghrelin ablation and GHS-R ablation in ob/ob mice [98], (4) the controversy could be also due to differences in experimental design (different doses, different times of observation, mode of injection, in vitro versus in vivo experiments, etc.). This is obvious in one study that tested the effect of different concentration of ghrelin on insulin release.…”

Section: Effects Of Ghrelin and Hexarelin On Insulin Secretion And Glmentioning

confidence: 99%

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

et al. 2015

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Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase ( JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulinproducing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases. Disciplines Medicine and Health Sciences Publication DetailsMosa, R., Zhang, Z., Shao, R., Deng, C., Chen, J. & Chen, C. (2015). Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases. Endocrine, 49 (2) AbstractGhrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration redu...

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Ablation of ghrelin receptor in leptin-deficient ob/ob mice has paradoxical effects on glucose homeostasis when compared with ablation of ghrelin in ob/ob mice

Cited by 39 publications

References 61 publications

Ghrelin

Ghrelin

Addition of crude glycerin to pig diets: sow and litter performance, and metabolic and feed intake regulating hormones

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

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