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Fetal hyperglycemia changes human preadipocyte function in adult life

Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line; Kelstrup, Louise; Houshmand-ØRegaard, Azadeh; Schrölkamp, Maren; Schultz, Heidi Schiøler; Scheele, Camilla; Pedersen, Bente Klarlund and Ling, Charlotte LU , et al. (2017) In Journal of Clinical Endocrinology and Metabolism 102(4). p.1141-1150
Abstract

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... (More)

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.

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Journal of Clinical Endocrinology and Metabolism
volume
102
issue
4
pages
10 pages
publisher
The Endocrine Society
external identifiers
  • scopus:85017329683
  • wos:000402195300006
ISSN
0021-972X
DOI
10.1210/jc.2016-3907
language
English
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yes
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fb316b03-59cd-44dc-8289-671a7a68a7ce
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2017-05-23 10:36:51
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2018-01-07 12:04:52
@article{fb316b03-59cd-44dc-8289-671a7a68a7ce,
  abstract     = {<p>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.</p>},
  author       = {Hansen, Ninna Schiøler and Strasko, Klaudia Stanislawa and Hjort, Line and Kelstrup, Louise and Houshmand-ØRegaard, Azadeh and Schrölkamp, Maren and Schultz, Heidi Schiøler and Scheele, Camilla and Pedersen, Bente Klarlund and Ling, Charlotte and Clausen, Tine Dalsgaard and Damm, Peter and Vaag, Allan and Broholm, Christa},
  issn         = {0021-972X},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {1141--1150},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Fetal hyperglycemia changes human preadipocyte function in adult life},
  url          = {http://dx.doi.org/10.1210/jc.2016-3907},
  volume       = {102},
  year         = {2017},
}