Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes – Role of insulin and IGF-I receptors

Bäck, Karolina; Brännmark, Cecilia; Strålfors, Peter; Arnqvist, Hans J.

doi:10.1016/j.mce.2011.04.005

Cited by 28 publications

(22 citation statements)

References 36 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Integrin ␤ 5, which directly interacts with ␣ -actinin ( 58 ), promotes the commitment of mesenchymal precursor cells to the adipogenic lineage in vitro ( 59,60 ), and the induction of this process is associated with increased expression of collagen IV ( 60 ) actin-binding heat shock protein that modulates actin fi lament dynamics in vivo ( 62 ). Hence, these data, combined with the fi ndings of Arner and colleagues ( 10 ), plus the decreased IGF1R mRNA levels in FCHL adipose tissue samples ( Table 2 ) that are indicative of reduced numbers of preadipocytes ( 63,64 ), suggest that FCHL-lipid abnormalities may develop, at least in part, from dysfunction of the complex developmental pathway that produces mature adipocytes.…”

Section: Discussionmentioning

confidence: 91%

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients

Horswell

Fryer

Hutchison

et al. 2013

Journal of Lipid Research

View full text Add to dashboard Cite

Familial combined hyperlipidemia (FCHL) is a common, complex genetic disorder characterized by a pernicious lipoprotein profi le that markedly increases the risk of premature coronary heart disease (CHD) ( 1-3 ). Affected individuals within families display elevated levels of serum cholesterol and/or triglyceride, plus raised apoB ( 1,(4)(5)(6)(7)(8). Patients may also exhibit high concentrations of cholesterol-enriched VLDL, triglyceride-enriched-HDL and small dense LDL ( 2, 3 ). Precise defi nition, however, is somewhat contentious, refl ecting etiological uncertainty.Abstract The purpose of this study was to determine the core biological processes perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a distinctive FCHL transcriptome, characterized by gene expression changes regulating fi ve overlapping systems: the cytoskeleton, cell adhesion and extracellular matrix; vesicular traffi cking; lipid homeostasis; and cell cycle and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells, CDKN2B knockdown induced C/EBP ␣ expression and lipid accumulation. The minor allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the human miRNA-323b-5p. A miR323b-5p mimic signifi cantly reduced endogenous CDKN2B protein levels and the activity of a CDKN2B 3 ′ UTR luciferase reporter carrying the rs1063192 C allele. Although the allele displayed suggestive evidence of association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family studies suggest the association between increased CDKN2B expression and FCHL-lipid abnormalities is driven by factors external to this gene locus. In conclusion, from a comparative annotation analysis of two separate FCHL adipose tissue transcriptomes and a subsequent focus on CDKN2B, we propose that dysfunctional adipogenesis forms an integral part of FCHL pathogenesis. -Horswell, S.

show abstract

Section: Discussionmentioning

confidence: 91%

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients

Horswell

Fryer

Hutchison

et al. 2013

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Insulin‐like growth factor‐II‐stimulated glucose uptake has been studied extensively in cellular systems. IGF‐II increased glucose uptake into 3T3‐L1 adipocytes and human adipocytes, albeit less potently than insulin or IGF‐I. The difference in potency may be attributed to IGF‐II acting through the IGF‐1R which binds it with relatively low affinity.…”

Section: Physiological Effects Of Igf‐iimentioning

confidence: 96%

Insulin‐like growth factor‐II: its role in metabolic and endocrine disease

Livingstone

Borai

2014

Clinical Endocrinology

114

View full text Add to dashboard Cite

SummaryInsulin-like growth factor-II (IGF-II) is a widely expressed 7Á5 kDa mitogenic peptide hormone. Although it is abundant in serum, understanding of its physiological role is limited compared with that of IGF-I. IGF-II regulates foetal development and differentiation, but its role in adults is less well understood. Evidence suggests roles in a number of tissues including skeletal muscle, adipose tissue, bone and ovary. Altered IGF-II expression has been observed in metabolic conditions, notably obesity, diabetes and the polycystic ovary syndrome. This article summarizes what is known about the actions of IGF-II and its dysregulation in metabolic and endocrine diseases. The possible causes and consequences of dysregulation are discussed along with the implications for diagnostic tests and future research.

show abstract

“…In in vitro systems, differentiation is initiated by exposure to IGF-I or high concentrations of insulin, the latter acting as a surrogate IGF-I receptor activator. In addition, IGF-I can influence insulin signaling through the insulin receptor (2,22). Therefore, regulation of IGF action by PAPP-A in a depot-specific manner could be highly relevant for adipose tissue function.…”

mentioning

confidence: 99%

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Conover

Harstad

Tchkonia

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Conover CA, Harstad SL, Tchkonia T, Kirkland JL. Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet. Am J Physiol Endocrinol Metab 305: E1145-E1153, 2013. First published September 17, 2013 doi:10.1152/ajpendo.00405.2013.-Accumulation of visceral fat, more so than subcutaneous fat, is strongly associated with severe metabolic complications. However, the factors regulating depot-specific adipogenesis are poorly understood. In this study, we show differential expression of pregnancy-associated plasma protein-A (PAPP-A), a secreted regulator of local insulin-like growth factor (IGF) action, in adipose tissue of mice. PAPP-A mRNA expression was fivefold higher in visceral (mesenteric) fat compared with subcutaneous (inguinal, subscapular), perirenal, and brown fat of mice. To investigate the possible role of depot-specific PAPP-A expression in fat accumulation, wild-type (WT) and PAPP-A knockout (KO) mice were fed a high-fat diet (HFD) for up to 20 wk. Adipocyte size increased in subcutaneous and perirenal depots similarly in WT and PAPP-A KO mice. However, fat cell size and in vivo lipid uptake were significantly reduced in mesenteric fat of PAPP-A KO compared with WT mice. After 20 wk on HFD, phosphorylation of AKT, a downstream signaling intermediate of IGF-I and insulin receptor activation, was significantly decreased by 50% in mesenteric compared with subcutaneous fat in WT mice, but was significantly increased threefold in mesenteric compared with subcutaneous fat in PAPP-A KO mice. This appeared to be because of enhanced insulinstimulated signaling in mesenteric fat of PAPP-A KO mice. These data establish fat depot-specific expression of PAPP-A and indicate preferential impact of PAPP-A deficiency on visceral fat in the mouse that is associated with enhanced insulin receptor signaling. Thus, PAPP-A may be a potential target for treatment and/or prevention strategies for visceral obesity and related morbidities.

show abstract

Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes – Role of insulin and IGF-I receptors

Cited by 28 publications

References 36 publications

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients

CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients

Insulin‐like growth factor‐II: its role in metabolic and endocrine disease

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Contact Info

Product

Resources

About