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Charlotte Ling

Charlotte Ling

Professor

Charlotte Ling

Fetal hyperglycemia changes human preadipocyte function in adult life

Author

  • Ninna Schiøler Hansen
  • Klaudia Stanislawa Strasko
  • Line Hjort
  • Louise Kelstrup
  • Azadeh Houshmand-ØRegaard
  • Maren Schrölkamp
  • Heidi Schiøler Schultz
  • Camilla Scheele
  • Bente Klarlund Pedersen
  • Charlotte Ling
  • Tine Dalsgaard Clausen
  • Peter Damm
  • Allan Vaag
  • Christa Broholm

Summary, in English

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.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-04-01

Language

English

Pages

1141-1150

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

102

Issue

4

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Epigenetics

ISBN/ISSN/Other

  • ISSN: 0021-972X