Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus
Program in Molecular Medicine; Department of Obstetrics and Gynecology; Department of Pediatrics; Graduate School of Biomedical Sciences; Biomedical Imaging Group; School of Medicine; Clinical Translational Research Pathway
Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Female Urogenital Diseases and Pregnancy Complications | Obstetrics and Gynecology
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.
DOI of Published Version
Diabetologia. 2015 Sep;58(9):2106-14. doi: 10.1007/s00125-015-3662-0. Epub 2015 Jun 13. Link to article on publisher's site
Rojas-Rodriguez, Raziel; Moore Simas, Tiffany A.; Lifshitz, Lawrence M.; Bellve, Karl D.; Min, So-Yun; Pires, Jacqueline; Leung, Katherine; Boeras, Crina; Sert, Aylin; Draper, Jacqueline T.; and Corvera, Silvia, "Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus" (2015). Open Access Articles. 2617.