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Dysregulation of Placental Lipid Hydrolysis by High-Fat/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice

Kuentzel, Katharina B. LU orcid ; Bradić, Ivan ; Mihalič, Zala N. ; Korbelius, Melanie ; Rainer, Silvia ; Pirchheim, Anita ; Kargl, Julia and Kratky, Dagmar (2022) In International Journal of Molecular Sciences 23(20). p.1-13
Abstract
Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal... (More)
Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. Placentae of HF/HCD-fed mice with and without GDM were more efficient, indicating increased nutrient transfer to the fetus. The increased activity of placental CE but not TG hydrolases in placentae of dams fed HF/HCD with or without GDM resulted in upregulated cholesterol export to the fetus and placental TG accumulation. Our results indicate that HF/HCD-induced dysregulation of placental lipid hydrolysis contributes to fetal hepatic lipid accumulation and possibly to fetal overgrowth, at least in mice (Less)
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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
International Journal of Molecular Sciences
volume
23
issue
20
article number
12286
pages
1 - 13
publisher
MDPI AG
external identifiers
  • scopus:85140989187
  • pmid:36293139
ISSN
1422-0067
DOI
10.3390/ijms232012286
language
English
LU publication?
no
id
170e5b1c-9c81-410a-b6ba-1376cce240b8
date added to LUP
2022-10-17 10:53:00
date last changed
2023-01-17 03:00:24
@article{170e5b1c-9c81-410a-b6ba-1376cce240b8,
  abstract     = {{Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. Placentae of HF/HCD-fed mice with and without GDM were more efficient, indicating increased nutrient transfer to the fetus. The increased activity of placental CE but not TG hydrolases in placentae of dams fed HF/HCD with or without GDM resulted in upregulated cholesterol export to the fetus and placental TG accumulation. Our results indicate that HF/HCD-induced dysregulation of placental lipid hydrolysis contributes to fetal hepatic lipid accumulation and possibly to fetal overgrowth, at least in mice}},
  author       = {{Kuentzel, Katharina B. and Bradić, Ivan and Mihalič, Zala N. and Korbelius, Melanie and Rainer, Silvia and Pirchheim, Anita and Kargl, Julia and Kratky, Dagmar}},
  issn         = {{1422-0067}},
  language     = {{eng}},
  number       = {{20}},
  pages        = {{1--13}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Dysregulation of Placental Lipid Hydrolysis by High-Fat/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice}},
  url          = {{http://dx.doi.org/10.3390/ijms232012286}},
  doi          = {{10.3390/ijms232012286}},
  volume       = {{23}},
  year         = {{2022}},
}