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Rigshospitalet - a part of Copenhagen University Hospital
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Fetal Hyperglycemia Changes Human Preadipocyte Function in Adult Life

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Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood.

Design: In total, we recruited 206 adult offspring comprising the two fetal hyperglycemic groups, O-GDM and O-T1DM, and, as a control group, offspring from the background population (O-BP). Subcutaneous fat biopsies were obtained and preadipocyte cell cultures were established from adult male O-GDM (n = 18, age 30.1 ± 2.5 years), O-T1DM (n = 18, age 31.6 ± 2.2 years), and O-BP (n = 16; age, 31.5 ± 2.7 years) and cultured in vitro.

Main Outcome Measures: First, we studied in vivo adipocyte histology. Second, we studied in vitro preadipocyte leptin secretion, gene expression, and LEP DNA methylation. This was studied in combination with in vitro preadipocyte lipogenesis, lipolysis, and mitochondrial respiration.

Results: We show that subcutaneous adipocytes from O-GDM are enlarged compared with O-BP adipocytes. Preadipocytes isolated from male O-GDM and O-T1DM and cultured in vitro displayed decreased LEP promoter methylation, increased leptin gene expression, and elevated leptin secretion throughout differentiation, compared with adipocytes established from male O-BP. In addition, the preadipocytes demonstrated functional defects including decreased maximal mitochondrial capacity with increased lipolysis and decreased ability to store fatty acids when challenged with 3 days of extra fatty acid supply.

Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume102
Issue number4
Pages (from-to)1141-1150
Number of pages10
ISSN0021-972X
DOIs
Publication statusPublished - 1 Apr 2017

    Research areas

  • Adipocytes, Adult, Adult Children, Case-Control Studies, Cells, Cultured, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetes, Gestational, Disease Susceptibility, Female, Fetal Diseases, Humans, Hyperglycemia, Lipolysis, Male, Pregnancy, Pregnancy in Diabetics, Prenatal Exposure Delayed Effects, Risk Factors, Journal Article

ID: 50651579