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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

Analysis of capillary density, collagen content and angiogenic potential in OM and abdominal SQ AT. (a) Representative images of capillary density in Rhodamine-lectin UEA-1-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c) Capillary density, shown as % of area (b) and as % of area × mean adipocyte size (c), in OM (coloured symbols) and SQ (white symbols) AT taken from individuals with NGT (circles), GDM (squares) and type 2 diabetes (triangles). Symbols show the means for each individual and lines represent the mean and SEM of all individuals. *p < 0.05 for indicated comparisons. (d) Representative examples of AT sections stained with picrosirius red. (e) Intensity of picrosirius red staining; symbols and lines are as described in (b) and (c). (f) Representative examples of capillary growth in AT. (g) Capillary growth area density; symbols and lines are as described in (b) and (c). *p < 0.05 for indicated comparisons
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Fig2: Analysis of capillary density, collagen content and angiogenic potential in OM and abdominal SQ AT. (a) Representative images of capillary density in Rhodamine-lectin UEA-1-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c) Capillary density, shown as % of area (b) and as % of area × mean adipocyte size (c), in OM (coloured symbols) and SQ (white symbols) AT taken from individuals with NGT (circles), GDM (squares) and type 2 diabetes (triangles). Symbols show the means for each individual and lines represent the mean and SEM of all individuals. *p < 0.05 for indicated comparisons. (d) Representative examples of AT sections stained with picrosirius red. (e) Intensity of picrosirius red staining; symbols and lines are as described in (b) and (c). (f) Representative examples of capillary growth in AT. (g) Capillary growth area density; symbols and lines are as described in (b) and (c). *p < 0.05 for indicated comparisons

Mentions: In parallel with the growth of adipocytes, the capillary network of AT must expand to sustain adipocyte function [36, 37]. Moreover, the vasculature of AT is a developmental niche for adipocyte precursors [38] and adequate angiogenesis may be a prerequisite for adipocyte hyperplasia. Capillary density was measured in lectin-stained whole mounts (Fig. 2a–c). The mean area of lectin staining (as % of total area) in OM AT was 21.3% (SD 5.0%; n = 11) in individuals with NGT, 13.2% (SD 4.8%; n = 5) in those with GDM and 16.6% (SD 4.5%; n = 3) in those with type 2 diabetes, with a statistically significance difference between the NGT and GDM group (p = 0.013). The mean area of lectin staining in SQ AT was 20.3% (SD 5.0%; n = 18) in individuals with NGTs, 13.6% (SD 3.9%; n = 5) in those with GDM and 16.5% (SD 2.2%; n = 3) in those with type 2 diabetes, with a statistically significant difference between the NGT and GDM group (p = 0.039). Differences in capillary density could not be attributed to changes in adipocyte size, as the product of capillary density and adipocyte size remained significantly different (Fig. 2c). To explore other alterations in AT associated with metabolic disease, such as fibrosis [39], we analysed fixed sectioned tissue for collagen content using picrosirius red (Fig. 2d, e). No significant differences were detected between groups, possibly due to the lower BMI and early onset of metabolic disease in this population compared with previously studied bariatric surgery populations [39, 40].Fig. 2


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)

Analysis of capillary density, collagen content and angiogenic potential in OM and abdominal SQ AT. (a) Representative images of capillary density in Rhodamine-lectin UEA-1-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c) Capillary density, shown as % of area (b) and as % of area × mean adipocyte size (c), in OM (coloured symbols) and SQ (white symbols) AT taken from individuals with NGT (circles), GDM (squares) and type 2 diabetes (triangles). Symbols show the means for each individual and lines represent the mean and SEM of all individuals. *p < 0.05 for indicated comparisons. (d) Representative examples of AT sections stained with picrosirius red. (e) Intensity of picrosirius red staining; symbols and lines are as described in (b) and (c). (f) Representative examples of capillary growth in AT. (g) Capillary growth area density; symbols and lines are as described in (b) and (c). *p < 0.05 for indicated comparisons
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Analysis of capillary density, collagen content and angiogenic potential in OM and abdominal SQ AT. (a) Representative images of capillary density in Rhodamine-lectin UEA-1-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c) Capillary density, shown as % of area (b) and as % of area × mean adipocyte size (c), in OM (coloured symbols) and SQ (white symbols) AT taken from individuals with NGT (circles), GDM (squares) and type 2 diabetes (triangles). Symbols show the means for each individual and lines represent the mean and SEM of all individuals. *p < 0.05 for indicated comparisons. (d) Representative examples of AT sections stained with picrosirius red. (e) Intensity of picrosirius red staining; symbols and lines are as described in (b) and (c). (f) Representative examples of capillary growth in AT. (g) Capillary growth area density; symbols and lines are as described in (b) and (c). *p < 0.05 for indicated comparisons
Mentions: In parallel with the growth of adipocytes, the capillary network of AT must expand to sustain adipocyte function [36, 37]. Moreover, the vasculature of AT is a developmental niche for adipocyte precursors [38] and adequate angiogenesis may be a prerequisite for adipocyte hyperplasia. Capillary density was measured in lectin-stained whole mounts (Fig. 2a–c). The mean area of lectin staining (as % of total area) in OM AT was 21.3% (SD 5.0%; n = 11) in individuals with NGT, 13.2% (SD 4.8%; n = 5) in those with GDM and 16.6% (SD 4.5%; n = 3) in those with type 2 diabetes, with a statistically significance difference between the NGT and GDM group (p = 0.013). The mean area of lectin staining in SQ AT was 20.3% (SD 5.0%; n = 18) in individuals with NGTs, 13.6% (SD 3.9%; n = 5) in those with GDM and 16.5% (SD 2.2%; n = 3) in those with type 2 diabetes, with a statistically significant difference between the NGT and GDM group (p = 0.039). Differences in capillary density could not be attributed to changes in adipocyte size, as the product of capillary density and adipocyte size remained significantly different (Fig. 2c). To explore other alterations in AT associated with metabolic disease, such as fibrosis [39], we analysed fixed sectioned tissue for collagen content using picrosirius red (Fig. 2d, e). No significant differences were detected between groups, possibly due to the lower BMI and early onset of metabolic disease in this population compared with previously studied bariatric surgery populations [39, 40].Fig. 2

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