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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 adipocyte size in OM and abdominal SQ AT. (a) Representative images of H&E-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c). Size distribution of adipocytes from OM (b) or SQ (c) AT. Plots show the means and SEM at each bin size of women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Arrow points to peak in region of larger adipocyte size in tissues from GDM and type 2 diabetes. Insets depict the paired signed rank difference between the histograms. (d) Mean adipocyte size from OM (coloured symbols) and SQ (white symbols) AT from women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Symbols show the means of each individual and lines represent the means and SEM of all individuals. *p < 0.05 and ***p < 0.001 for indicated comparisons. (e–h) Linear regression analyses: BMI vs mean OM adipocyte size (r2 = 0.038; p = 0.433) (e); gestational weight gain (GWG) vs mean OM adipocyte size (r2 = 0.149; p = 0.651) (f); mean OM adipocyte size vs serum glucose (r2 = 0.505; p = 0.0009) (g) and maximal OM adipocyte size vs serum glucose (r2 = 0.568; p = 0.0003) (h). White circles, NGT; black circles, GDM
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Fig1: Analysis of adipocyte size in OM and abdominal SQ AT. (a) Representative images of H&E-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c). Size distribution of adipocytes from OM (b) or SQ (c) AT. Plots show the means and SEM at each bin size of women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Arrow points to peak in region of larger adipocyte size in tissues from GDM and type 2 diabetes. Insets depict the paired signed rank difference between the histograms. (d) Mean adipocyte size from OM (coloured symbols) and SQ (white symbols) AT from women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Symbols show the means of each individual and lines represent the means and SEM of all individuals. *p < 0.05 and ***p < 0.001 for indicated comparisons. (e–h) Linear regression analyses: BMI vs mean OM adipocyte size (r2 = 0.038; p = 0.433) (e); gestational weight gain (GWG) vs mean OM adipocyte size (r2 = 0.149; p = 0.651) (f); mean OM adipocyte size vs serum glucose (r2 = 0.505; p = 0.0009) (g) and maximal OM adipocyte size vs serum glucose (r2 = 0.568; p = 0.0003) (h). White circles, NGT; black circles, GDM

Mentions: Adipocyte size was quantified (Fig. 1a). The mean cell size in OM AT was 4,163 μm2 (SD 1,380 μm2; n = 13) in individuals with NGT, 7,482 μm2 (SD 2,980 μm2; n = 5) in those with GDM and 6,849 μm2 (SD 1,060 μm2; n = 3) in those with type 2 diabetes, with a statistically significant difference between the NGT and GDM group (p = 0.019). OM AT from women with GDM contained an increased number of large adipocytes (as shown by a peak in the size distribution histogram above the mean value in Fig. 1b, arrows). The difference in the frequency distribution between NGT and GDM was statistically significant (p = 0.028). A similar trend was seen in samples from three type 2 diabetes cases, also plotted but not analysed due to the small sample size. The mean cell size in SQ AT was 7,066 μm2 (SD 2,612 μm2; n = 15) in individuals with NGT, 9,045 μm2 (SD 2,340 μm2; n = 5) in those with GDM and 9,102 μm2 (SD 2,503 μm2; n = 3) in those with type 2 diabetes. The difference between the NGT and GDM group was not statistically significant (p = 0.178). A trend for larger adipocyte numbers in SQ tissue from individuals with GDM was seen in the size distribution histograms (Fig. 1c), but the difference did not reach statistical significance. In women with NGT, adipocytes from OM AT (mean size 4,178 μm2; SD 1,440 μm2; n = 12) were significantly smaller (p = 0.0005) than those from SQ AT (mean size 7,581 μm2; SD 2,672 μm2; n = 12); this difference was eliminated in GDM (p = 0.125) due to the increase in mean OM adipocyte size (mean size 7,482 μm2; SD 2,980 μm2; n = 5) (Fig. 1d). The increase in mean OM adipocyte size in individuals with GDM could not be explained by an increase in BMI (Fig. 1e) or gestational weight gain (Fig. 1f) but was highly correlated with serum glucose levels (Fig. 1g), as was the maximal OM adipocyte size (Fig. 1h). This finding is consistent with those of previous studies in non-pregnant individuals in which large adipocytes are associated with dyslipidaemia as well as glucose and insulin abnormalities [34, 35], revealing a similarity between a central AT feature in GDM and type 2 diabetes.Fig. 1


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 adipocyte size in OM and abdominal SQ AT. (a) Representative images of H&E-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c). Size distribution of adipocytes from OM (b) or SQ (c) AT. Plots show the means and SEM at each bin size of women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Arrow points to peak in region of larger adipocyte size in tissues from GDM and type 2 diabetes. Insets depict the paired signed rank difference between the histograms. (d) Mean adipocyte size from OM (coloured symbols) and SQ (white symbols) AT from women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Symbols show the means of each individual and lines represent the means and SEM of all individuals. *p < 0.05 and ***p < 0.001 for indicated comparisons. (e–h) Linear regression analyses: BMI vs mean OM adipocyte size (r2 = 0.038; p = 0.433) (e); gestational weight gain (GWG) vs mean OM adipocyte size (r2 = 0.149; p = 0.651) (f); mean OM adipocyte size vs serum glucose (r2 = 0.505; p = 0.0009) (g) and maximal OM adipocyte size vs serum glucose (r2 = 0.568; p = 0.0003) (h). White circles, NGT; black circles, GDM
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Related In: Results  -  Collection

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Fig1: Analysis of adipocyte size in OM and abdominal SQ AT. (a) Representative images of H&E-stained AT taken from individuals with NGT, GDM or type 2 diabetes (T2DM). Scale bar, 200 μm. (b, c). Size distribution of adipocytes from OM (b) or SQ (c) AT. Plots show the means and SEM at each bin size of women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Arrow points to peak in region of larger adipocyte size in tissues from GDM and type 2 diabetes. Insets depict the paired signed rank difference between the histograms. (d) Mean adipocyte size from OM (coloured symbols) and SQ (white symbols) AT from women with NGT (blue circles), GDM (red squares) and type 2 diabetes (green triangles). Symbols show the means of each individual and lines represent the means and SEM of all individuals. *p < 0.05 and ***p < 0.001 for indicated comparisons. (e–h) Linear regression analyses: BMI vs mean OM adipocyte size (r2 = 0.038; p = 0.433) (e); gestational weight gain (GWG) vs mean OM adipocyte size (r2 = 0.149; p = 0.651) (f); mean OM adipocyte size vs serum glucose (r2 = 0.505; p = 0.0009) (g) and maximal OM adipocyte size vs serum glucose (r2 = 0.568; p = 0.0003) (h). White circles, NGT; black circles, GDM
Mentions: Adipocyte size was quantified (Fig. 1a). The mean cell size in OM AT was 4,163 μm2 (SD 1,380 μm2; n = 13) in individuals with NGT, 7,482 μm2 (SD 2,980 μm2; n = 5) in those with GDM and 6,849 μm2 (SD 1,060 μm2; n = 3) in those with type 2 diabetes, with a statistically significant difference between the NGT and GDM group (p = 0.019). OM AT from women with GDM contained an increased number of large adipocytes (as shown by a peak in the size distribution histogram above the mean value in Fig. 1b, arrows). The difference in the frequency distribution between NGT and GDM was statistically significant (p = 0.028). A similar trend was seen in samples from three type 2 diabetes cases, also plotted but not analysed due to the small sample size. The mean cell size in SQ AT was 7,066 μm2 (SD 2,612 μm2; n = 15) in individuals with NGT, 9,045 μm2 (SD 2,340 μm2; n = 5) in those with GDM and 9,102 μm2 (SD 2,503 μm2; n = 3) in those with type 2 diabetes. The difference between the NGT and GDM group was not statistically significant (p = 0.178). A trend for larger adipocyte numbers in SQ tissue from individuals with GDM was seen in the size distribution histograms (Fig. 1c), but the difference did not reach statistical significance. In women with NGT, adipocytes from OM AT (mean size 4,178 μm2; SD 1,440 μm2; n = 12) were significantly smaller (p = 0.0005) than those from SQ AT (mean size 7,581 μm2; SD 2,672 μm2; n = 12); this difference was eliminated in GDM (p = 0.125) due to the increase in mean OM adipocyte size (mean size 7,482 μm2; SD 2,980 μm2; n = 5) (Fig. 1d). The increase in mean OM adipocyte size in individuals with GDM could not be explained by an increase in BMI (Fig. 1e) or gestational weight gain (Fig. 1f) but was highly correlated with serum glucose levels (Fig. 1g), as was the maximal OM adipocyte size (Fig. 1h). This finding is consistent with those of previous studies in non-pregnant individuals in which large adipocytes are associated with dyslipidaemia as well as glucose and insulin abnormalities [34, 35], revealing a similarity between a central AT feature in GDM and type 2 diabetes.Fig. 1

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