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Fetal Hyperglycemia Changes Human Preadipocyte Function in Adult Life

Ninna Schiøler Hansen1,2,3, Klaudia Stanislawa Strasko1,2, Line Hjort1,2,4

  • 1Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, 2200 Denmark.

The Journal of Clinical Endocrinology and Metabolism
|February 17, 2017
PubMed

Insights

Offspring exposed to high blood sugar during pregnancy show altered fat cells. These changes in preadipocytes suggest an increased risk for metabolic disease later in life.

Area of Science:

  • Endocrinology and Metabolism
  • Epigenetics
  • Cell Biology

Background:

  • Maternal hyperglycemia during pregnancy, including gestational diabetes mellitus (GDM) and type 1 diabetes mellitus (T1DM), leads to fetal exposure to hyperglycemia.
  • Offspring of these pregnancies (O-GDM and O-T1DM) have an elevated risk of developing metabolic diseases in adulthood.

Purpose of the Study:

  • To investigate the long-term effects of fetal hyperglycemia on adipocyte development and function in adult offspring.
  • To identify potential epigenetic and functional alterations in preadipocytes from individuals exposed to in utero hyperglycemia.

Main Methods:

  • Recruited adult offspring from pregnancies with GDM, T1DM, and a control population (offspring from background population - O-BP).
  • Obtained subcutaneous fat biopsies and established preadipocyte cell cultures from male O-GDM, O-T1DM, and O-BP.
  • Analyzed in vivo adipocyte histology, in vitro preadipocyte leptin secretion, gene expression, LEP DNA methylation, lipogenesis, lipolysis, and mitochondrial respiration.

Main Results:

  • Subcutaneous adipocytes from O-GDM were enlarged compared to O-BP.
  • Preadipocytes from O-GDM and O-T1DM exhibited decreased LEP promoter methylation, increased leptin gene expression, and elevated leptin secretion.
  • These preadipocytes displayed functional deficits: reduced maximal mitochondrial capacity, increased lipolysis, and impaired fatty acid storage.

Conclusions:

  • Individuals exposed to fetal hyperglycemia show intrinsic epigenetic and functional changes in their preadipocytes.
  • These alterations suggest a predisposition to metabolic disease in adulthood.
  • Fetal exposure to hyperglycemia has lasting impacts on adipose tissue development and function.
Abstract

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