IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

Siddals, Kirk; Westwood, Melissa; Gibson, John M.; White, Anne

doi:10.1677/joe.0.1740289

Cited by 48 publications

(33 citation statements)

References 27 publications

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“…However, IM subjects showed a tendency towards increased fat mass and reduced adiponectin in comparison to the UM group. This finding could be consistent with a role of IGF2 in fat tissue growth and development [43,44,45,46]. …”

Section: Discussionsupporting

confidence: 85%

IGF2 Methylation Is Associated with Lipid Profile in Obese Children

et al. 2013

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Aim: Our aim was to investigate the relationships between the degree of IGF2 methylation and the metabolic status in obese children and adolescents. Subjects and Methods: Eighty-five obese subjects aged 11.6 ± 2.1 years were studied. Anthropometry, metabolic parameters, blood pressure and body composition were assessed. DNA methylation analysis was performed by restriction enzyme digestion assay. The study population was subdivided into two groups according to the percentage of IGF2 cytidine-guanosine (CpG) island methylation. Results: Twenty-two subjects showed intermediate methylation (a percentage of CpG site methylation comprised between 10 and 60%), 56 were hypomethylated (percentage of methylation lower than 10%), and only 1 showed a high rate of hypermethylation (percentage of methylation above 60%). Children with intermediate methylation showed significantly higher levels of triglycerides (107.6 ± 41.99 vs. 76.6 ± 30.18 mg/dl, p < 0.005) and a higher triglyceride/high-density lipoprotein-cholesterol ratio (2.23 ± 0.98 vs. 1.79 ± 0.98, p < 0.02) compared with hypomethylated children. Conclusions: These preliminary findings show for the first time a relationship between IGF2 methylation pattern and lipid profile in obese children. Although the correlation does not imply causation, if our findings are confirmed in further studies, IGF2 methylation might represent an epigenetic marker of metabolic risk.

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Section: Discussionsupporting

confidence: 85%

IGF2 Methylation Is Associated with Lipid Profile in Obese Children

et al. 2013

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“…In primary rat adipocytes, Ͼ30 nM (480 ng/ml) leptin almost completely inhibits metabolic activities associated with insulin, such as stimulation of glucose transport, glycogen synthase, lipogenesis, and protein synthesis (41). Insulin is a mitogenic factor and has been shown to increase proliferation and differentiation of preadipocytes in cell lines (52,54). Leptin and insulin activate many of the same pathways, such as mitogenactivated protein kinase (MAPK), signal transducer and activator of transcription 1 and 3 (STAT1 and STAT3), and phosphatidylinositol 3-kinase (7); therefore, high concentrations of leptin could activate these pathways and interfere with insulin signaling.…”

Section: Discussionmentioning

confidence: 99%

Direct and indirect effects of leptin on preadipocyte proliferation and differentiation

Wagoner¹,

Hausman²,

Harris³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Leptin has been shown to reduce body fat in vivo. Adipocytes express the leptin receptor; therefore, it is realistic to expect a direct effect of leptin on adipocyte growth and metabolism. In vitro studies examining the effect of leptin on adipocyte metabolism require supraphysiological doses of the protein to see a decrease in lipogenesis or stimulation of lipolysis, implying an indirect action of leptin. It also is possible that leptin reduces adipose mass by inhibiting preadipocyte proliferation (increase in cell number) and/or differentiation (lipid filling). Thus we determined direct and indirect effects of leptin on preadipocyte proliferation and differentiation in vitro. We tested the effect of leptin (0-500 ng/ml), serum from leptin-infused rats (0.25% by volume), and adipose tissue-conditioned medium from leptin-infused rats (0-30% by volume) on preadipocyte proliferation and differentiation in a primary culture of cells from male Sprague-Dawley rat adipose tissue. Leptin (50 ng/ml) stimulated proliferation of preadipocytes (P<0.05), but 250 and 500 ng leptin/ml inhibited proliferation of both preadipocyte and stromal vascular cell fractions (P<0.01), as measured by [3H]thymidine incorporation. Serum from leptin-infused rats inhibited proliferation of the adipose and stromal vascular fractions (P=0.01), but adipose tissue-conditioned medium had no effect on proliferation of either cell fraction. None of the treatments changed preadipocyte differentiation as measured by sn-glycerophosphate dehydrogenase activity. These results suggest that leptin could inhibit preadipocyte proliferation by modifying release of a factor from tissue other than adipose tissue.

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“…IGFBP-1 concentrations are higher in women than men [17]. Phosphorylated forms of IGFBP-1 acutely inhibit IGF effects on 3T3-L1 preadipocytes and adipocytes [18]. Specific proteolysis of IGFBP-1 generates IGF-binding fragments with reduced IGF-II-stimulated glucose uptake in muscle [19].…”

Section: Role Of the Igf System In Normal Metabolismmentioning

confidence: 99%

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

Lewitt

Dent

Hall

2014

JCM

115

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The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target.

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IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

Cited by 48 publications

References 27 publications

<b><i>IGF2</i></b> Methylation Is Associated with Lipid Profile in Obese Children

<b><i>IGF2</i></b> Methylation Is Associated with Lipid Profile in Obese Children

Direct and indirect effects of leptin on preadipocyte proliferation and differentiation

The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

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