TY - JOUR
T1 - Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity
AU - Serafim, Teresa L.
AU - Cunha-Oliveira, Teresa
AU - Deus, Claudia M.
AU - Sardão, Vilma A.
AU - Cardoso, Ines M.
AU - Yang, Shanshan
AU - Odhiambo, John F.
AU - Ghnenis, Adel B.
AU - Smith, Ashley M.
AU - Li, Junfei
AU - Nathanielsz, Peter W.
AU - Ford, Stephen P.
AU - Oliveira, Paulo J.
N1 - Funding Information:
This paper is dedicated to the memory of the late Stephen Ford (University of Wyoming). The authors are grateful to Ablat Tuerxun (University of Wyoming), Tatiana Martins and Catarina Morais (CNC) for their technical support. This work was funded by European Regional Development Fund (ERFD) through the Operational Programme Competitiveness Factors (COMPETE) and Portuguese national funds by FCT?Foundation for Science and Technology (PTDC/DTP-DES/1082/2014, POCI-01-0145-FEDER-016657, POCI-01-0145-FEDER-029297, UIDB/04539/2020, and UID/NEU/04539/2019) and NIH (P01 HD 21350, R01HD070096-01A1). This work was also supported by National Institutes of Health R01-HD070096-01-A1.
Funding Information:
This paper is dedicated to the memory of the late Stephen Ford (University of Wyoming). The authors are grateful to Ablat Tuerxun (University of Wyoming), Tatiana Martins and Catarina Morais (CNC) for their technical support. This work was funded by European Regional Development Fund (ERFD) through the Operational Programme Competitiveness Factors (COMPETE) and Portuguese national funds by FCT—Foundation for Science and Technology (PTDC/DTP‐DES/1082/2014, POCI‐01‐0145‐FEDER‐016657, POCI‐01‐0145‐FEDER‐029297, UIDB/04539/2020, and UID/NEU/04539/2019) and NIH (P01 HD 21350, R01HD070096‐01A1). This work was also supported by National Institutes of Health R01‐HD070096‐01‐A1.
Publisher Copyright:
© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd
PY - 2021/2
Y1 - 2021/2
N2 - Background: Changes in the nutritional environment in utero induced by maternal obesity (MO) lead to foetal metabolic dysfunction predisposing offspring to later-life metabolic diseases. Since mitochondria play a crucial role in hepatic metabolism and function, we hypothesized that MO prior to conception and throughout pregnancy programmes foetal sheep liver mitochondrial phenotype. Material and methods: Ewes ate an obesogenic diet (150% requirements; MO), or 100% requirements (CTR), from 60 days prior to conception. Foetal livers were removed at 0.9 gestation. We measured foetal liver mitochondrial DNA copy number, activity of superoxide dismutase, cathepsins B and D and selected protein content, total phospholipids and cardiolipin and activity of mitochondrial respiratory chain complexes. Results: A significant decrease in activities of mitochondrial complexes I, II-III and IV, but not aconitase, was observed in MO. In the antioxidant machinery, there was a significant increase in activity of total superoxide dismutase (SOD) and SOD2 in MO. However, no differences were found regarding autophagy-related protein content (p62, beclin-I, LC3-I, LC3-II and Lamp2A) and cathepsin B and D activities. A 21.5% decrease in total mitochondrial phospholipid was observed in MO. Conclusions: The data indicate that MO impairs foetal hepatic mitochondrial oxidative capacity and affects total mitochondrial phospholipid content. In addition, MO affects the regulation of foetal liver redox pathways, indicating metabolic adaptations to the higher foetal lipid environment. Consequences of in utero programming of foetal hepatic metabolism may persist and compromise mitochondrial bioenergetics in later life, and increase susceptibility to metabolic diseases.
AB - Background: Changes in the nutritional environment in utero induced by maternal obesity (MO) lead to foetal metabolic dysfunction predisposing offspring to later-life metabolic diseases. Since mitochondria play a crucial role in hepatic metabolism and function, we hypothesized that MO prior to conception and throughout pregnancy programmes foetal sheep liver mitochondrial phenotype. Material and methods: Ewes ate an obesogenic diet (150% requirements; MO), or 100% requirements (CTR), from 60 days prior to conception. Foetal livers were removed at 0.9 gestation. We measured foetal liver mitochondrial DNA copy number, activity of superoxide dismutase, cathepsins B and D and selected protein content, total phospholipids and cardiolipin and activity of mitochondrial respiratory chain complexes. Results: A significant decrease in activities of mitochondrial complexes I, II-III and IV, but not aconitase, was observed in MO. In the antioxidant machinery, there was a significant increase in activity of total superoxide dismutase (SOD) and SOD2 in MO. However, no differences were found regarding autophagy-related protein content (p62, beclin-I, LC3-I, LC3-II and Lamp2A) and cathepsin B and D activities. A 21.5% decrease in total mitochondrial phospholipid was observed in MO. Conclusions: The data indicate that MO impairs foetal hepatic mitochondrial oxidative capacity and affects total mitochondrial phospholipid content. In addition, MO affects the regulation of foetal liver redox pathways, indicating metabolic adaptations to the higher foetal lipid environment. Consequences of in utero programming of foetal hepatic metabolism may persist and compromise mitochondrial bioenergetics in later life, and increase susceptibility to metabolic diseases.
KW - maternal obesity
KW - metabolic programming
KW - mitochondrial bioenergetics
KW - mitochondrial phospholipids
KW - oxidative stress
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U2 - 10.1111/eci.13375
DO - 10.1111/eci.13375
M3 - Article
C2 - 32780417
AN - SCOPUS:85090793029
VL - 51
JO - Archiv fur klinische Medizin
JF - Archiv fur klinische Medizin
SN - 0014-2972
IS - 2
M1 - e13375
ER -