scholarly journals The Effect of Growth Hormone on Lipid Accumulation or Maturation in Adipocytes

2016 ◽  
Vol 39 (6) ◽  
pp. 2135-2148 ◽  
Author(s):  
Yuchao Zhang ◽  
Hongsheng Yu ◽  
Peng Gao ◽  
Jicui Chen ◽  
Cong Yu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cdna Microarray ◽  
Lipid Accumulation ◽  
Lipid Synthesis ◽  
Epididymal Adipose Tissue ◽  
Gh Treatment ◽  
Gh Secretion ◽  
Expression Of Genes

Background: Adipogenesis of adipocytes includes two stages: initiation and maturation. Growth hormone (GH) secretion is decreased in obese subjects and GH levels are inversely correlated with abdominal fat mass. The effects of growth hormone (GH) on lipids accumulation or maturation of adipocytes remains elusive. Methods: In the present study, effect of GH on lipid accumulation in vitro and in vivo was examined. cDNA microarray, quantitative real time-PCR (qPCR) and western blotting was used to analyze the expression of genes related to adipocyte lipid accumulation or degradation in pre- or mature 3T3-F442A adipocytes treated with GH and in epididymal adipose tissue of C57BL/6 mice administrated with GH. Level of adiponectin in supernatants of cultured F442A adipocytes was determined by enzyme-linked immune-sorbent assay. Results: We found that in 3T3-F442A especially 6 days post initiation of adipogenesis, GH intervention resulted in decreased expression of adipocyte maturation regulators (C/EBPα, PPARγ) and prominent genes related to lipid synthesis such as FAS and FABP, while the expression of UCP1 was markedly enhanced. cDNA microarray analysis and qPCR showed that the expression of SOCS2 and Adipor2 was increased under GH-treatment in mature 3T3-F442A adipocytes. GH treatment increased the mRNA expression of adiponectin and UCP1 in mature adipocytes. The above results were confirmed by in vivo study. Conclusions: GH potentially negatively modulates the maturation and accumulation of lipid in adipocytes.

scholarly journals E3 ubiquitin ligase Grail promotes hepatic steatosis through Sirt1 inhibition

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Pei-Yao Liu ◽  
Cheng-Cheung Chen ◽  
Chia-Ying Chin ◽  
Te-Jung Liu ◽  
Wen-Chiuan Tsai ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Sirtuin 1 ◽  
Nonalcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Hepatic Fat ◽  
Underlying Mechanisms

AbstractIn obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

scholarly journals 905 FASN prevents immunogenicity of irradiated glioblastoma by inhibiting ER stress

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A950-A950
Author(s):  
Mara De Martino ◽  
Camille Daviaud ◽  
Claire Vanpouille-Box
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Immune Escape ◽  
De Novo ◽  
Lipid Synthesis ◽  
Adult Brain ◽  
Immune Recognition

BackgroundGlioblastoma (GBM) is the most aggressive and incurable adult brain tumor. Radiation therapy (RT) is an essential modality for GBM treatment and is recognized to stimulate anti-tumor immunity by inducing immunogenic cell death (ICD) subsequent to endoplasmic reticulum (ER) stress. However, RT also exacerbates potent immunosuppressive mechanisms that facilitate immune evasion. Notably, increased de novo lipid synthesis by the fatty acid synthase (FASN) is emerging as a mechanism of therapy resistance and immune escape. Here, we hypothesize that RT induces FASN to promote GBM survival and evade immune recognition by inhibiting ER stress and ICD.MethodsTo determine if lipid synthesis is altered in response to RT, we first assessed FASN expression by western blot (WB) and lipid accumulation by BODIPY staining in murine (CT2A and GL261) and human (U118) GBM cell lines. Next, FASN expression was blocked in CT2A cells using CRISPR-Cas9 or an inducible shRNA directed against Fasn to evaluate ICD and ER stress markers by ELISA, WB, and electron microscopy. Finally, CT2AshFASN cells or its non-silencing control (CT2AshNS) were orthotopically implanted and FASN knockdown was induced by feeding the mice with doxycycline. The immune contexture was determined by in situ immunofluorescence (n=3/group). Remaining mice were followed for survival (n=7/group).ResultsWe found that in vitro irradiation of GBM cells induces lipid accumulation in a dose-dependent fashion; an effect that is magnified over time lasting at least 6/7 days. Consistent with these findings, FASN expression was upregulated in irradiated GBM cells. Confirming the role of FASN, RT-induced accumulation of lipids was reverted when GBM cells were incubated with a FASN inhibitor. Next, we found that FASN ablation in CT2A cells induces mitochondria disruption and was sufficient to increase the expression of the ER stress makers BIP and CHOP. Along similar lines, shFASN enhances the secretion of the ICD markers HMGB1, IFN-beta and CXCL10 in irradiated CT2A cells. In vivo, CT2AshFASN tumors presented increased infiltration of CD11c+ cells and CD8+ T cells, consistent with prolonged mice survival (56 days vs. 28 days for CT2AshNS). Importantly, 43% of CT2AshFASN-bearing mice remained tumor-free for more than 70 days, while none of the CT2AshNS-bearing mice survived.ConclusionsAltogether, our data suggest that FASN-mediated lipid synthesis is an important mechanism to prevent ER stress, ICD, and anti-tumor immune responses in GBM. While much work remains to be done, our data propose FASN as a novel therapeutic target to overcome immunosuppression and sensitize GBM to immunotherapies.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

scholarly journals A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 331 ◽  
Author(s):  
Xin Wang ◽  
Min Liu ◽  
Guo He Cai ◽  
Yan Chen ◽  
Xiao Chen Shi ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Early Stage ◽  
Lipid Synthesis ◽  
Clonal Expansion ◽  
Inhibitory Effect ◽  
Limiting Factor ◽  
Stat3 Signaling Pathway ◽  
Mitotic Clonal Expansion

The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity.

A possible relationship between serum transferrin, growth hormone secretion and height velocity in children

1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job
Keyword(s):  
Growth Hormone ◽  
Growth Regulation ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Height Velocity ◽  
Obese Children ◽  
Gh Secretion ◽  
Growth Promoting

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.

scholarly journals Role of Prolactin and Growth Hormone on Thymus Physiology

1998 ◽  
Vol 6 (3-4) ◽  
pp. 317-323 ◽  
Author(s):  
Valéria De Mello-Coelho ◽  
Wilson Savino ◽  
Marie-Catherine Postel-Vinay ◽  
Mireille Dardenne
Keyword(s):  
Growth Hormone ◽  
Epithelial Cells ◽  
Cell Types ◽  
Pituitary Hormones ◽  
Thymic Epithelial Cells ◽  
Double Positive ◽  
Gh Treatment ◽  
Thymic Hormone

Intrathymic T-cell differentiation is under the control of the thymic microenvironment, which acts on maturing thymocytes via membrane as well as soluble products. Increasing data show that this process can be modulated by classical hormones, as exemplified herein by prolactin (PRL) and growth hormone (GH), largely secreted by the pituitary gland.Both PRL and GH stimulate the secretion of thymulin, a thymic hormone produced by thymic epithelial cells. Conversely, low levels of circulating thymulin parallel hypopituitary states. Interestingly, the enhancing effects of GH on thymulin seem to be mediated by insulinlike growth factor (IGF-1) since they can be abrogated with anti-IGF-1 or anti-IGF-l-receptor antibodies. The influence of PRL and GH on the thymic epithelium is pleiotropic: PRL enhancesin vivothe expression of high-molecular-weight cytokeratins and stimulatesin vitroTEC proliferation, an effect that is shared by GH and IGF-1.Differentiating T cells are also targets for the intrathymic action of PRL and GH.In vivoinoculation of a rat pituitary cell line into old rats results in restoration of the thymus, including differentiation of CD4-CD8-thymocytes into CD4+CD8+cells. Furthermore, PRL may regulate the maintenance of thymocyte viability during the double-positive stage of thymocyte differentiation.Injections of GH into aging mice increase total thymocyte numbers and the percentage of CD3-bearing cells, as well as the Concanavalin-A mitogenic response and IL-6 production by thymocytes. Interestingly, similar findings are observed in animals treated with IGF-1. Lastly, the thymic hypoplasia observed in dwarf mice can be reversed with GH treatment.In keeping with the data summarized earlier is the detection of receptors for PRL and GH on both thymocytes and thymic epithelial cells. Importantly, recent studies indicate that both cell types can produce PRL and GH intrathymically. Similarly, production of IGF-1 and expression of a corresponding receptor has also been demonstrated.In conclusion, these data strongly indicate that the thymus is physiologically under control of pituitary hormones PRL and GH. In addition to the classical endocrine pathway, paracrine and autocrine circuits are probably implicated in such control.

Glucocorticoid modulation of growth hormone secretion in vitro. Evidence for a biphasic effect on GH-releasing hormone mediated release

1987 ◽  
Vol 114 (4) ◽  
pp. 465-469 ◽  
Author(s):  
Gian Paolo Ceda ◽  
Robert G. Davis ◽  
Andrew R. Hoffman
Keyword(s):  
Growth Hormone ◽  
Prolonged Exposure ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Glucocorticoid Action

Abstract. Glucocorticoids have been shown to have both stimulatory and suppressive effects on GH secretion in vitro and in vivo. In order to study the kinetics of glucocorticoid action on the somatotrope, cultured rat pituitary cells were exposed to dexamethasone for varying periods of time. During short-term incubations (≤ 4 h), dexamethasone inhibited GHRH and forskolin-elicited GH secretion, but during longer incubation periods, the glucocorticoid enhanced both basal and GHRH-stimulated GH release. The inhibitory effect of brief dexamethasone exposure was also seen in cells which previously had been exposed to dexamethasone. In addition, growth hormone secretion from cultured rat and human somatotropinoma cells was inhibited by a brief exposure to dexamethasone. Thus, the nature of glucocorticoid action on the isolated cultured somatotrope is biphasic, with brief exposure inhibiting, and more prolonged exposure stimulating GH secretion.

Tri-iodothyronine inhibition of thyrotrophin-releasing hormone-induced growth hormone release from the chicken adenohypophysis in vitro

1990 ◽  
Vol 126 (1) ◽  
pp. 75-81 ◽  
Author(s):  
S. Harvey
Keyword(s):  
Growth Hormone ◽  
Hormone Release ◽  
Growth Hormone Release ◽  
Direct Effects ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Site Of Action

ABSTRACT Tri-iodothyronine (T3) had no effect on the basal level of GH release from chicken hemipituitary glands perifused in vitro. The GH response to TRH was, however, markedly suppressed following exposure to T3. Suppression of TRH-stimulated GH secretion was observed after a 2-h preincubation with T3, and was induced, in a dose-related way, by 0·01–10 μmol T3/l. Exposure to T3 also reduced the effectiveness of TRH, at concentrations of 0·001–10 μg/ml, to stimulate GH release. These results demonstrate that, in addition to a hypothalamic site of action, T3 is likely to suppress GH secretion in vivo by direct effects on pituitary GH release. Journal of Endocrinology (1990) 126, 75–81

scholarly journals Comprehensive evaluation of the metabolic effects of porcine CRTC3 overexpression on subcutaneous adipocytes with metabolomic and transcriptomic analyses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiaqi Liu ◽  
Jie Li ◽  
Wentao Chen ◽  
Xintao Xie ◽  
Xingang Chu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Comprehensive Evaluation ◽  
Adenosine Monophosphate ◽  
Fat Deposition ◽  
Metabolic Effects ◽  
Rna Seq ◽  
Expression Of Genes

Abstract Background Meat quality is largely driven by fat deposition, which is regulated by several genes and signaling pathways. The cyclic adenosine monophosphate (cAMP) -regulated transcriptional coactivator 3 (CRTC3) is a coactivator of cAMP response element binding protein (CREB) that mediates the function of protein kinase A (PKA) signaling pathway and is involved in various biological processes including lipid and energy metabolism. However, the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet. Here, we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs (a local fatty breed in China) and Duroc×Landrace×Yorkshire (DLY, a lean breed) pigs in vivo. The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing (RNA-seq). Results Porcine CRTC3 expression is associated with fat deposition in vivo. In addition, CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes. According to the metabolomic analysis, CRTC3 overexpression induced significant changes in adipocyte lipid, amino acid and nucleotide metabolites in vitro. The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis, fatty acid metabolism and glycerophospholipid metabolism in vitro. Conclusions We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes. Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.

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