Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice.

  title={Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice.},
  author={Emil Egecioglu and Mikael Bjursell and Anna Ljungberg and Suzanne L. Dickson and John J. Kopchick and G{\"o}ran Bergstr{\"o}m and Lennart Svensson and Jan Oscarsson and Jan Törnell and M Bohlooly-y},
  journal={American journal of physiology. Endocrinology and metabolism},
  volume={290 2},
We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR-/- and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on GHR signaling. GHR-/- mice were also analyzed with respect to serum levels of lipoproteins… 

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Effects of growth hormone-releasing hormone gene targeted ablation on ghrelin-induced feeding.

  • L. RecinellaS. Leone L. Brunetti
  • Biology, Medicine
    Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society
  • 2017

Role of endogenous ghrelin in growth hormone secretion, appetite regulation and metabolism

Substantial data have implicated ghrelin as an important regulator of feeding behavior and energy equilibrium and this effect is mediated through hypothalamic neuropeptide Y (NPY) and Agouti-related peptide (AgRP).

Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications

Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that gh Relin may have a redundant role in the regulation of food intake.

Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion.

The existence of a new central nervous system-based neuroendocrine circuit, regulating metabolic homeostasis of adipose tissue, is suggested by the effect of central ghrelin administration on lipid metabolism in lipogenic tissues (liver and WAT) in the absence of GH.

The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice.

The GH/IGF-1 axis is important in determining not only adipose tissue accrual but also the inflammatory response to HFD, however, how hypothalamic inflammation/gliosis is defined will determine whether it can be considered a common feature of HFD-induced obesity.

Ghrelin-Induced Food Intake, But not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice.

The findings indicate that GHR signaling in the brain is required for the orexigenic effect of ghrelin, independently of GH action on ARH AgRP/NPY neurons.

Effects of isolated GH deficiency on adipose tissue, feeding and adipokines in mice.

Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells

GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic–pituitary–adrenal axis, acute stress response or anxiety in mice.

The Pentapeptide RM-131 Promotes Food Intake and Adiposity in Wildtype Mice but Not in Mice Lacking the Ghrelin Receptor

The data show that in wildtype mice RM-131 potently promotes weight gain and adiposity through stimulation of food intake, however, RM- 131 fails to affect food intake and body weight in mice lacking the GHR, underlining that the anabolic effects ofRM-131 are mediated via the ghrelin receptor in mice.



Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.

GH overexpression in the CNS results in hyperphagia-induced obesity indicating a dual effect of GH with a central stimulation of appetite and a peripheral lipolytic effect.

Ghrelin induces adiposity in rodents

It is proposed that ghrelin, in addition to its role in regulating GH secretion, signals the hypothalamus when an increase in metabolic efficiency is necessary, suggesting an involvement in regulation of energy balance.

Importance of melanin-concentrating hormone receptor for the acute effects of ghrelin.

Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats.

The effects of chronic intracerebroventricular treatment with ghrelin on metabolic factors and on neuropeptide genes that are expressed in hypothalamic neurons that have been previously shown to express the GHS-R and to regulate food consumption are determined.

A role for ghrelin in the central regulation of feeding

It is shown that ghrelin is involved in the hypothalamic regulation of energy homeostasis and probably has a function in growth regulation by stimulating feeding and release of growth hormone.

Chronic Changes in Peripheral Growth Hormone Levels Do Not Affect Ghrelin Stomach mRNA Expression and Serum Ghrelin Levels in Three Transgenic Mouse Models

These data support previous observations that the stomach is the main source of circulating ghrelin, and indicate that stomach gh Relin mRNA expression and serum concentrations of ghrel in are not affected by chronic changes in peripheral GH/insulin‐like growth factor‐I levels/action.

Comparing adiposity profiles in three mouse models with altered GH signaling.

Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice.

It is concluded that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.

Pituitary and testicular function in growth hormone receptor gene knockout mice.

The results indicate that the lack of GHRs (with GH resistance and lack of IGF-I secretion) induces hyperprolactinemia and alters the effect of GnRH on LH secretion as well as testicular function, which influences pituitary and gonadal functions in male mice.

The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic.

Evidence is provided that the ghrelin-sensitive circuits in the hypothalamus are dynamically regulated by central insulin and leptin action.