Limits...
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

Potential role of IGFBP5 in AT expansion in pregnancy. (a) In non-pregnant women, IGFBPs sequester IGF-1 and IGF-2. Proteolysis of IGFBPs releases the growth factors, which act on AT vasculature and maintain tissue homeostasis. (b) In pregnancy, the induction of IGFBP5 increases the amount of sequestered IGF-1. The pregnancy-specific protease PAPP-A degrades IGFBP5 to release IGFs, promoting angiogenesis, pre-adipocyte proliferation and hyperplastic expansion
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4526585&req=5

Fig4: Potential role of IGFBP5 in AT expansion in pregnancy. (a) In non-pregnant women, IGFBPs sequester IGF-1 and IGF-2. Proteolysis of IGFBPs releases the growth factors, which act on AT vasculature and maintain tissue homeostasis. (b) In pregnancy, the induction of IGFBP5 increases the amount of sequestered IGF-1. The pregnancy-specific protease PAPP-A degrades IGFBP5 to release IGFs, promoting angiogenesis, pre-adipocyte proliferation and hyperplastic expansion

Mentions: Previous studies from our group identified IGFBP4 as a potential key factor in AT expansion in response to a high-fat diet in mice [49]. The marked upregulation of IGFBP5 seen in AT from pregnant women supports a similar role for the IGF-1 signalling pathway in adult AT expansion. IGFBP5 binds IGF-1 and IGF-2 with high affinity and has been shown in cell and animal models to inhibit signalling by sequestering these growth factors [23]. However, IGFBP5 also binds to the extracellular matrix of tissues, and can thereby serve as a local reservoir of IGF-1 [23]. The concurrent expression of IGFBP5 in AT and secretion of PAPP-A by the placenta suggests a mechanism whereby the local concentration of IGF-1 is increased in AT through interaction with IGFBP5 and release in response to PAPP-A secretion, thereby coordinating placental function with maternal AT expansion (Fig. 4). Abnormalities in this mechanism could potentially lead to impaired AT expansion and to lipotoxicity and metabolic disruption manifesting as GDM. This hypothesis is consistent with previous studies in which type 2 diabetes has been associated with abnormalities in SQ AT levels of the IGF-1 receptor and IGFBP3 [50]. While our current study is limited by sample size and by differences in age and BMI between groups, the large magnitude of the results presented support a new model to explore the mechanism of AT expansion in pregnancy and its role in the aetiology of GDM.Fig. 4


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)

Potential role of IGFBP5 in AT expansion in pregnancy. (a) In non-pregnant women, IGFBPs sequester IGF-1 and IGF-2. Proteolysis of IGFBPs releases the growth factors, which act on AT vasculature and maintain tissue homeostasis. (b) In pregnancy, the induction of IGFBP5 increases the amount of sequestered IGF-1. The pregnancy-specific protease PAPP-A degrades IGFBP5 to release IGFs, promoting angiogenesis, pre-adipocyte proliferation and hyperplastic expansion
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4526585&req=5

Fig4: Potential role of IGFBP5 in AT expansion in pregnancy. (a) In non-pregnant women, IGFBPs sequester IGF-1 and IGF-2. Proteolysis of IGFBPs releases the growth factors, which act on AT vasculature and maintain tissue homeostasis. (b) In pregnancy, the induction of IGFBP5 increases the amount of sequestered IGF-1. The pregnancy-specific protease PAPP-A degrades IGFBP5 to release IGFs, promoting angiogenesis, pre-adipocyte proliferation and hyperplastic expansion
Mentions: Previous studies from our group identified IGFBP4 as a potential key factor in AT expansion in response to a high-fat diet in mice [49]. The marked upregulation of IGFBP5 seen in AT from pregnant women supports a similar role for the IGF-1 signalling pathway in adult AT expansion. IGFBP5 binds IGF-1 and IGF-2 with high affinity and has been shown in cell and animal models to inhibit signalling by sequestering these growth factors [23]. However, IGFBP5 also binds to the extracellular matrix of tissues, and can thereby serve as a local reservoir of IGF-1 [23]. The concurrent expression of IGFBP5 in AT and secretion of PAPP-A by the placenta suggests a mechanism whereby the local concentration of IGF-1 is increased in AT through interaction with IGFBP5 and release in response to PAPP-A secretion, thereby coordinating placental function with maternal AT expansion (Fig. 4). Abnormalities in this mechanism could potentially lead to impaired AT expansion and to lipotoxicity and metabolic disruption manifesting as GDM. This hypothesis is consistent with previous studies in which type 2 diabetes has been associated with abnormalities in SQ AT levels of the IGF-1 receptor and IGFBP3 [50]. While our current study is limited by sample size and by differences in age and BMI between groups, the large magnitude of the results presented support a new model to explore the mechanism of AT expansion in pregnancy and its role in the aetiology of GDM.Fig. 4

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