Increased placental mitochondrial fusion in gestational diabetes mellitus: an adaptive mechanism to optimize feto-placental metabolic homeostasis?

BMJ Open Diabetes Research & Care
Joelcio AbbadeIsabella Caniggia

Abstract

Gestational diabetes mellitus (GDM), a common pregnancy disorder, increases the risk of fetal overgrowth and later metabolic morbidity in the offspring. The placenta likely mediates these sequelae, but the exact mechanisms remain elusive. Mitochondrial dynamics refers to the joining and division of these organelles, in attempts to maintain cellular homeostasis in stress conditions or alterations in oxygen and fuel availability. These remodeling processes are critical to optimize mitochondrial function, and their disturbances characterize diabetes and obesity. Herein we show that placental mitochondrial dynamics are tilted toward fusion in GDM, as evidenced by transmission electron microscopy and changes in the expression of key mechanochemical enzymes such as OPA1 and active phosphorylated DRP1. In vitro experiments using choriocarcinoma JEG-3 cells demonstrated that increased exposure to insulin, which typifies GDM, promotes mitochondrial fusion. As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Pl...Continue Reading

Citations

Sep 1, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Luis SobreviaReinaldo Marín
Sep 19, 2020·Endocrinology·Manasi DasNicholas J G Webster
Feb 10, 2021·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Jelena MeiniläSaila Koivusalo
Jan 29, 2021·Scientific Reports·Anna Maria NuzzoAlessandro Rolfo
Dec 19, 2020·Placenta·Minhui Lu, Amanda Nancy Sferruzzi-Perri
Mar 31, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Anjali JadhavSadhana Joshi
May 16, 2021·Cellular Signalling·Yuliya FakhrDenise G Hemmings
Jul 2, 2021·Molecular and Cellular Biochemistry·Lissette Sanchez-Aranguren, Sarah Nadeem

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Methods Mentioned

BETA
transmission electron microscopy
protein assay
cesarean section
confocal microscopy

Software Mentioned

Volocity
SPSS Statistics
ImageQuant
Image J
ImageJ
GraphPad Prism

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