Inhibition of Adipogenesis by Ghrelin

Zhang, Weizhen; Zhao, Lili; Lin, Theodore R.; Chai, Biaoxin; Fan, Yongyi; Gantz, Ira; Mulholland, Michael W.

doi:10.1091/mbc.e03-09-0657

Cited by 105 publications

(87 citation statements)

References 39 publications

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“…Ghrelin binding activity is demonstrated in 3T3-L1 cells by radiolabeled ghrelin, although RT-PCR detected no signal for the ghrelin receptor (273). Moreover, both ghrelin and des-acyl ghrelin bind to H9c2 cardiomyocytes, which do not express the ghrelin receptor (15).…”

Section: A the Ghrelin Receptor Familymentioning

confidence: 95%

Ghrelin: Structure and Function

Kojima

Kangawa²

2005

Physiological Reviews

1,616

1,176

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Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G protein-coupled receptor whose ligand has only been discovered recently. Using a reverse pharmacology paradigm with a stable cell line expressing GHS-R, we purified an endogenous ligand for GHS-R from rat stomach and named it “ghrelin,” after a word root (“ghre”) in Proto-Indo-European languages meaning “grow.” Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary might be regulated not only by hypothalamic GH-releasing hormone, but also by ghrelin derived from the stomach. In addition, ghrelin stimulates appetite by acting on the hypothalamic arcuate nucleus, a region known to control food intake. Ghrelin is orexigenic; it is secreted from the stomach and circulates in the bloodstream under fasting conditions, indicating that it transmits a hunger signal from the periphery to the central nervous system. Taking into account all these activities, ghrelin plays important roles for maintaining GH release and energy homeostasis in vertebrates.

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Section: A the Ghrelin Receptor Familymentioning

confidence: 95%

Ghrelin: Structure and Function

Kojima

Kangawa²

2005

Physiological Reviews

1,616

1,176

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“…[19][20][21] Nonetheless, these data are not univocal, as other authors have reported that overexpression of ghrelin inhibits adipocyte differentiation in 3T3-L1 adipocytes, and that the genetic deletion of ghrelin or its receptor in mice induces thymic adipogenesis. 22,23 These contradictory observations raise some questions regarding the involvement of ghrelin in the control of adipocyte metabolism. Therefore, the aim of this study was to explore the potential differences in circulating ghrelin and desacyl ghrelin concentrations in normal weight, obesity and obesity-associated T2D, as well as to investigate the possibility of a direct peripheral effect of acylated and desacyl ghrelin on human adipocytes.…”

Section: Introductionmentioning

confidence: 99%

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

et al. 2009

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Objectives: The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans. Methods: Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1-1000 pmol l À1 ) on adipogenesis was determined in vitro in omental adipocytes. Results: Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPARg (peroxisome proliferator-activated receptor g) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation. Conclusions: Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity.

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“…Its actions include a role in appetite regulation and obesity (Wren et al 2001), while the evidence regarding its influence on adipogenesis is contradictory (Zhang et al 2004a). Energy homeostasis is directly associated with reproductive function and the importance of ghrelin in a range of reproductive processes, including steroid hormone regulation and embryo development, has recently been demonstrated (Barreiro & Tena-Sempere 2004).…”

Section: Introductionmentioning

confidence: 99%

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

Jeffery

Murray²,

Yeh³

et al. 2005

Endocr Relat Cancer

111

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While oestrogen, progesterone and growth factors, including growth hormone (GH), are clearly implicated in the pathogenesis of breast cancer, there is now evidence that the newly described ghrelin axis is also involved. The aims of this study were to investigate the expression of the ghrelin axis in breast cancer tissues and cell lines and to examine the effect of ghrelin on breast cancer cell proliferation in vitro. Ghrelin and its functional receptor, the growth hormone secretagogue receptor (GHSR) type 1a, were expressed in normal breast tissue and breast cancer specimens and cell lines. In contrast, the truncated GHSR type 1b isoform was exclusively expressed in breast carcinoma, suggesting that it has potential as a diagnostic marker. Ghrelin treatment significantly increases the proliferation of the MDA-MB-435 and MDA-MB-231 breast cancer cell lines in vitro. In addition, we have described the expression of a human preproghrelin isoform, exon 3-deleted preproghrelin, which encodes mature ghrelin plus a novel C-terminal peptide. Quantitative RT-PCR was used to demonstrate that this mRNA isoform is highly expressed in the MDA-MB-435 metastatic breast cancer cell line relative to the benign MCF-10A breast epithelial cell line. The unique C-terminal peptide of exon 3-deleted preproghrelin is expressed in the glandular epithelium of breast cancer tissues, with high-grade carcinoma exhibiting the strongest immunoreactivity. The data presented here suggest that components of the ghrelin axis may represent novel markers for breast cancer and potential therapeutic targets.

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Inhibition of Adipogenesis by Ghrelin

Cited by 105 publications

References 39 publications

Ghrelin: Structure and Function

Ghrelin: Structure and Function

Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

Expression and function of the ghrelin axis, including a novel preproghrelin isoform, in human breast cancer tissues and cell lines

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