Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring.

Autor: Adekunbi DA; Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, Texas, USA., Yang B; Research Imaging Institute, Long School of Medicine, The University of Texas Health Science Center at San Antonio, Ant Texas, USA., Huber HF; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA., Riojas AM; Research Imaging Institute, Long School of Medicine, The University of Texas Health Science Center at San Antonio, Ant Texas, USA., Moody AJ; Research Imaging Institute, Long School of Medicine, The University of Texas Health Science Center at San Antonio, Ant Texas, USA., Li C; Texas Pregnancy and Life-course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA., Olivier M; Center for Precision Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Nathanielsz PW; Texas Pregnancy and Life-course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA., Clarke GD; Research Imaging Institute, Long School of Medicine, The University of Texas Health Science Center at San Antonio, Ant Texas, USA., Cox LA; Center for Precision Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Salmon AB; Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, Texas, USA.; Geriatric Research Education and Clinical Center, Audie L. Murphy Hospital, Southwest Veterans Health Care System, San Antonio, Texas, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 May 05. Date of Electronic Publication: 2024 May 05.
DOI: 10.1101/2024.05.02.592246
Abstrakt: We previously demonstrated in baboons that maternal undernutrition (MUN), achieved by 70 % of control nutrition, impairs fetal liver function, but long-term changes associated with aging in this model remain unexplored. Here, we assessed clinical phenotypes of liver function, mitochondrial bioenergetics, and protein abundance in adult male and female baboons exposed to MUN during pregnancy and lactation and their control counterparts. Plasma liver enzymes were assessed enzymatically. Liver glycogen, choline, and lipid concentrations were quantified by magnetic resonance spectroscopy. Mitochondrial respiration in primary hepatocytes under standard culture conditions and in response to metabolic (1 mM glucose) and oxidative (100 µM H 2 O 2 ) stress were assessed with Seahorse XFe96. Hepatocyte mitochondrial membrane potential (MMP) and protein abundance were determined by tetramethylrhodamine ethyl ester staining and immunoblotting, respectively. Liver enzymes and metabolite concentrations were largely unaffected by MUN, except for higher aspartate aminotransferase levels in MUN offspring when male and female data were combined. Oxygen consumption rate, extracellular acidification rate, and MMP were significantly higher in male MUN offspring relative to control animals under standard culture. However, in females, cellular respiration was similar in control and MUN offspring. In response to low glucose challenge, only control male hepatocytes were resistant to low glucose-stimulated increase in basal and ATP-linked respiration. H 2 O 2 did not affect hepatocyte mitochondrial respiration. Protein markers of mitochondrial respiratory chain subunits, biogenesis, dynamics, and antioxidant enzymes were unchanged. Male-specific increases in mitochondrial bioenergetics in MUN offspring may be associated with increased energy demand in these animals. The similarity in systemic liver parameters suggests that changes in hepatocyte bioenergetics capacity precede detectable circulatory hepatic defects in MUN offspring and that the mitochondria may be an orchestrator of liver programming outcome.
Competing Interests: Competing Interest The authors declare no competing interest.
Databáze: MEDLINE
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