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Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

Rojas-Rodriguez R, Lifshitz LM, Bellve KD, Min SY, Pires J, Leung K, Boeras C, Sert A, Draper JT, Corvera S, Moore Simas TA - Diabetologia (2015)

Bottom Line: Mean OM and SQ capillary density was lower in GDM compared with NGT (p = 0.015).Capillary growth did not differ significantly between groups.The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA, 01605, USA.

ABSTRACT

Aims/hypothesis: During pregnancy, adipose tissue (AT) must expand to support the growing fetus and the future nutritional needs of the offspring. Limited expandability of AT is associated with insulin resistance, attributed to ectopic lipid deposition. This study aimed to investigate human AT expandability during pregnancy and its role in the pathogenesis of gestational diabetes mellitus (GDM).

Methods: This cross-sectional study of omental (OM) and subcutaneous (SQ) AT collected at Caesarean delivery included 11 pregnant and three non-pregnant women with normal glucose tolerance (NGT), five with GDM, three with type 2 diabetes mellitus. Adipocyte size, capillary density, collagen content and capillary growth were measured. Affymetrix arrays and real-time PCR studies of gene expression were performed.

Results: Mean OM adipocyte size was greater in women with GDM than in those with NGT (p = 0.004). Mean OM and SQ capillary density was lower in GDM compared with NGT (p = 0.015). Capillary growth did not differ significantly between groups. The most differentially expressed AT transcript when comparing non-pregnant and pregnant women corresponded to the IGF binding protein (IGFBP)-5, the expression levels of which was found by subsequent quantitative real-time PCR to be lower in women with GDM vs women with NGT (p < 0.0001).

Conclusions/interpretation: The relative OM adipocyte hypertrophy and decreased OM and SQ capillary density are consistent with impaired AT expandability in GDM. The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.

No MeSH data available.


Related in: MedlinePlus

AT gene expression in pregnancy and GDM. (a) Heat map of 22,000 genes, and specific expression values for IGFBP5, in AT from non-pregnant and pregnant women with NGT. Values for IGFBP5 (relative signal intensity) are shown. (b) Relationship between BMI and IGFBP5 levels in SQ (black triangles) and OM (white circles) AT from individuals used for the Affymetrix array. (c) Real-time PCR analysis of SQ AT from non-pregnant women with NGT (white bars), pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was IGFBP1. (d) Real-time PCR analysis of SQ AT from pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was FGF2. Adjusted p values: *p < 0.05, **p < 0.01 and ****p < 0.0001 for indicated comparisons
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Fig3: AT gene expression in pregnancy and GDM. (a) Heat map of 22,000 genes, and specific expression values for IGFBP5, in AT from non-pregnant and pregnant women with NGT. Values for IGFBP5 (relative signal intensity) are shown. (b) Relationship between BMI and IGFBP5 levels in SQ (black triangles) and OM (white circles) AT from individuals used for the Affymetrix array. (c) Real-time PCR analysis of SQ AT from non-pregnant women with NGT (white bars), pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was IGFBP1. (d) Real-time PCR analysis of SQ AT from pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was FGF2. Adjusted p values: *p < 0.05, **p < 0.01 and ****p < 0.0001 for indicated comparisons

Mentions: Total RNA was isolated using TRIzol (Life Technologies). Affymetrix (Santa Clara, CA, USA) protocols were followed for the preparation of cRNA, which was hybridised to HG-U133v2 Chips. Raw expression data collected from an Affymetrix HP GeneArrayScanner was normalised across all data sets using the RMA algorithm. Probes in which any condition resulted in raw expression values above 1,000 were included in the heat map shown in Fig. 3.


Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus.

Rojas-Rodriguez R, Lifshitz LM, Bellve KD, Min SY, Pires J, Leung K, Boeras C, Sert A, Draper JT, Corvera S, Moore Simas TA - Diabetologia (2015)

AT gene expression in pregnancy and GDM. (a) Heat map of 22,000 genes, and specific expression values for IGFBP5, in AT from non-pregnant and pregnant women with NGT. Values for IGFBP5 (relative signal intensity) are shown. (b) Relationship between BMI and IGFBP5 levels in SQ (black triangles) and OM (white circles) AT from individuals used for the Affymetrix array. (c) Real-time PCR analysis of SQ AT from non-pregnant women with NGT (white bars), pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was IGFBP1. (d) Real-time PCR analysis of SQ AT from pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was FGF2. Adjusted p values: *p < 0.05, **p < 0.01 and ****p < 0.0001 for indicated comparisons
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig3: AT gene expression in pregnancy and GDM. (a) Heat map of 22,000 genes, and specific expression values for IGFBP5, in AT from non-pregnant and pregnant women with NGT. Values for IGFBP5 (relative signal intensity) are shown. (b) Relationship between BMI and IGFBP5 levels in SQ (black triangles) and OM (white circles) AT from individuals used for the Affymetrix array. (c) Real-time PCR analysis of SQ AT from non-pregnant women with NGT (white bars), pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was IGFBP1. (d) Real-time PCR analysis of SQ AT from pregnant women with NGT (black bars) and pregnant women with GDM (grey bars). Values are normalised to the lowest expressed transcript in the NGT group, which was FGF2. Adjusted p values: *p < 0.05, **p < 0.01 and ****p < 0.0001 for indicated comparisons
Mentions: Total RNA was isolated using TRIzol (Life Technologies). Affymetrix (Santa Clara, CA, USA) protocols were followed for the preparation of cRNA, which was hybridised to HG-U133v2 Chips. Raw expression data collected from an Affymetrix HP GeneArrayScanner was normalised across all data sets using the RMA algorithm. Probes in which any condition resulted in raw expression values above 1,000 were included in the heat map shown in Fig. 3.

Bottom Line: Mean OM and SQ capillary density was lower in GDM compared with NGT (p = 0.015).Capillary growth did not differ significantly between groups.The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA, 01605, USA.

ABSTRACT

Aims/hypothesis: During pregnancy, adipose tissue (AT) must expand to support the growing fetus and the future nutritional needs of the offspring. Limited expandability of AT is associated with insulin resistance, attributed to ectopic lipid deposition. This study aimed to investigate human AT expandability during pregnancy and its role in the pathogenesis of gestational diabetes mellitus (GDM).

Methods: This cross-sectional study of omental (OM) and subcutaneous (SQ) AT collected at Caesarean delivery included 11 pregnant and three non-pregnant women with normal glucose tolerance (NGT), five with GDM, three with type 2 diabetes mellitus. Adipocyte size, capillary density, collagen content and capillary growth were measured. Affymetrix arrays and real-time PCR studies of gene expression were performed.

Results: Mean OM adipocyte size was greater in women with GDM than in those with NGT (p = 0.004). Mean OM and SQ capillary density was lower in GDM compared with NGT (p = 0.015). Capillary growth did not differ significantly between groups. The most differentially expressed AT transcript when comparing non-pregnant and pregnant women corresponded to the IGF binding protein (IGFBP)-5, the expression levels of which was found by subsequent quantitative real-time PCR to be lower in women with GDM vs women with NGT (p < 0.0001).

Conclusions/interpretation: The relative OM adipocyte hypertrophy and decreased OM and SQ capillary density are consistent with impaired AT expandability in GDM. The induction of adipose tissue IGFBP5 in pregnancy and its decrease in GDM point to the importance of the IGF-1 signalling pathway in AT expansion in pregnancy and GDM susceptibility.

No MeSH data available.


Related in: MedlinePlus