Elevated IGF2 prevents leptin induction and terminal adipocyte differentiation in hemangioma stem cells

Kleiman, Alexandra; Keats, Emily C.; Chan, Nancy; Khan, Zia A.

doi:10.1016/j.yexmp.2012.09.023

Cited by 21 publications

(18 citation statements)

References 36 publications

(42 reference statements)

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“…As detailed in the Introduction, the IGF system is integral to adipose tissue development with IGF1 and IGF2 having roles in adipocyte proliferation and differentiation (Holly et al 2006, Kleiman et al 2013), which in turn theoretically underlies a greater potential for enhanced fat mass. However, in the current early postnatal study, perirenal fat IGF ligand and receptor expression were inversely associated with adipocyte size, visceral fat mass and carcass fat content and positively associated with relative adipocyte number when these relationships were examined for the population as a whole.…”

Section: Prenatal Growth Gender and Perirenal Fat Gene Expressionmentioning

confidence: 99%

“…Evidence from inducible gene knockouts and from preadipocyte and stem cell culture studies supports a role for locally produced insulin-like growth factors (IGF1 and IGF2) in adipocyte proliferation and differentiation (Holly et al 2006, Kleiman et al 2013. IGF1 also plays a role in the modulation of energy balance in that its administration to hypophysectomised rats and to growth hormone (GH)-deficient humans reduces adipose tissue leptin expression and peripheral leptin concentrations respectively (Böni-Schnetzler et al 1996, Bianda et al 1997.…”

Section: Introductionmentioning

confidence: 99%

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Influence of birth weight and gender on lipid status and adipose tissue gene expression in lambs

Wallace

Milne

Aitken

et al. 2014

Journal of Molecular Endocrinology

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Intrauterine growth restriction (IUGR) is a risk factor for obesity, particularly when offspring are born into an unrestricted nutritional environment. In this study, we investigated the impact of IUGR and gender on circulating lipids and on expression of adipogenic, lipogenic and adipokine genes in perirenal adipose tissue. Singleton lambs born to overnourished adolescent dams were normal birth weight (N) or IUGR (32% lower birth weight due to placental insufficiency). IUGR lambs exhibited increased fractional growth rates but remained smaller than N lambs at necropsy (d77). At 48 days, fasting plasma triglycerides, non-esterified fatty acids and glycerol were elevated predominantly in IUGR males. Body fat content was independent of prenatal growth but higher in females than in males. In perirenal fat, relative to male lambs, females had larger adipocytes; higher lipoprotein lipase, fatty acid synthase and leptin and lower IGF1, IGF2, IGF1R, IGF2R and hormonesensitive lipase mRNA expression levels, and all were independent of prenatal growth category; peroxisome proliferator-activated receptor gamma and glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression were not affected by IUGR or gender. Adiposity indices were inversely related to G3PDH mRNA expression, and for the population as a whole the expression of IGF system genes in perirenal fat was negatively correlated with plasma leptin, fat mass and adipocyte size, and positively correlated with circulating IGF1 levels. Higher plasma lipid levels in IUGR males may predict later adverse metabolic health and obesity, but in early postnatal life gender has the dominant influence on adipose tissue gene expression, reflecting the already established sexual dimorphism in body composition.

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Section: Prenatal Growth Gender and Perirenal Fat Gene Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of birth weight and gender on lipid status and adipose tissue gene expression in lambs

Wallace

Milne

Aitken

et al. 2014

Journal of Molecular Endocrinology

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show abstract

“…We examined genes involved in adipocyte proliferation and differentiation, namely IGF1, IGF2, IGF1R, IGF2R (Holly et al 2006; Kleiman et al 2013), and peroxisome-proliferator-activated receptor-gamma ( PPARG) a transcriptional regulator playing a central role in adipocyte differentiation as well as co-ordinating genes involved in lipid deposition and metabolism (Semple et al 2006). These include lipogenic genes such as lipoprotein lipase ( LPL ), which enhances fatty acid uptake into adipocytes, fatty acid synthase ( FASN ), which catalyses fatty acid synthesis, and glycerol-3-phosphate dehydrogenase ( G3PDH ), which is involved in glyceroneogenesis, and lipolytic genes such as hormone sensitive lipase ( HSL ), which is involved in hydrolysis of stored triglycerides to release non-esterified fatty acids (NEFA).…”

Section: Introductionmentioning

confidence: 99%

Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Wallace¹,

Milne²,

Aitken³

et al. 2015

Journal of Molecular Endocrinology

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Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both associated with inadequate prenatal adipose tissue development. Here we investigated the impact of maternal undernutrition on expression of genes regulating fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145d). Singleton fetuses were taken from adolescent ewes fed control (C) intake to maintain adiposity throughout pregnancy or undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89 but by day 130 fetuses from UN dams were 17% lighter with lower PAT mass containing fewer unilocular adipocytes. Relative PAT expression of IGF1, IGF2, IGF2R and peroxisome-proliferator-activated receptor-gamma (PPARG) mRNA was lower in UN than in C, predominantly at day 89. Independent of maternal nutrition, PAT gene expression of PPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein-1 and prolactin receptor increased and IGF1, IGF2, IGF1R, IGF2R decreased between 89 and 130 days. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greater LPL and leptin mRNA than males, and LPL, leptin and PPARG mRNAs were decreased by UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than day 130. These data suggest that key genes regulating adipose tissue development and function are active from mid-gestation when they are sensitive to maternal undernutrition. This leads to reduced fetal adiposity by late pregnancy.

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“…Loss of imprinting of igf2 is a common feature in tumors seen in BeckwithWiedemann syndrome [13]. Recent studies have identified that IGF2 is highly expressed during the proliferative phase of hemangioma growth [14]. As IGF2 promotes development of fetal pancreatic beta cells, it is believed to be involved in some forms of diabetes mellitus [7,15].…”

Section: Introductionmentioning

confidence: 99%

Expression and efficient purification of tag-cleaved active recombinant human insulin-like growth factor-II from Escherichia coli

Hui

et al. 2015

Biotechnol Bioproc E

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Insulin-like growth factor-II (IGF2) is a growth factor for the control of cell proliferation and apoptosis. To explore the clinical use of human IGF2, an efficient method for production of a large amount of active recombinant hIGF2 is necessary. Human IGF2 cDNA was cloned into pET32 vector where it is under the control of an IPTGinducible T7 promoter. High level soluble thioredoxin (Trx)-hIGF2 fusion protein was produced at room temperature following IPTG induction, amounting up to 20% of the total soluble bacterial proteins. The recombinant TrxhIGF2 fusion protein was purified to an approximate 95% purity using Ni + -NTA affinity chromatography with an overall yield of 120 mg protein per liter of bacterial culture. After cleavage of the Trx fusion fragment by recombinant enterokinase, the tag-free recombinant hIGF2 protein (rhIGF2) was purified by passage through the Ni+-NTA affinity column again. Biological activity of the purified hIGF2 was determined by its ability to support NIH/3T3 cells proliferation and to activate AKT signaling pathways. Our results demonstrate that tag-free active rhIGF2 can easily be obtained for various applications from E. coli using the procedure described in this report.

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Elevated IGF2 prevents leptin induction and terminal adipocyte differentiation in hemangioma stem cells

Cited by 21 publications

References 36 publications

Influence of birth weight and gender on lipid status and adipose tissue gene expression in lambs

Influence of birth weight and gender on lipid status and adipose tissue gene expression in lambs

Undernutrition and stage of gestation influence fetal adipose tissue gene expression

Expression and efficient purification of tag-cleaved active recombinant human insulin-like growth factor-II from Escherichia coli

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