Low Protein Programming Causes Increased Mitochondrial Fusion and Decreased Oxygen Consumption in the Hepatocytes of Female Rats.
Vipin A VidyadharanChellakkan S BlessonDaren TanchicoAncizar BetancourtCraig SmithChandra YallampalliPublished in: Nutrients (2023)
The liver is one of the major organs involved in the regulation of glucose and lipid homeostasis. The effectiveness of metabolic activity in hepatocytes is determined by the quality and quantity of its mitochondria. Mitochondrial function is complex, and they act via various dynamic networks, which rapidly adapt to changes in the cellular milieu. Our present study aims to investigate the effects of low protein programming on the structure and function of mitochondria in the hepatocytes of adult females. Pregnant rats were fed with a control or isocaloric low-protein diet from gestational day 4 until delivery. A normal laboratory chow was given to all dams after delivery and to pups after weaning. The rats were euthanized at 4 months of age and the livers were collected from female offspring for investigating the mitochondrial structure, mtDNA copy number, mRNA, and proteins expression of genes associated with mitochondrial function. Primary hepatocytes were isolated and used for the analysis of the mitochondrial bioenergetics profiles. The mitochondrial ultrastructure showed that the in utero low-protein diet exposure led to increased mitochondrial fusion. Accordingly, there was an increase in the mRNA and protein levels of the mitochondrial fusion gene Opa1 and mitochondrial biogenesis genes Pgc1a and Essra, but Fis1, a fission gene, was downregulated. Low protein programming also impaired the mitochondrial function of the hepatocytes with a decrease in basal respiration ATP-linked respiration and proton leak. In summary, the present study suggests that the hepatic mitochondrial dysfunction induced by an in utero low protein diet might be a potential mechanism linking glucose intolerance and insulin resistance in adult offspring.
Keyphrases
- copy number
- oxidative stress
- binding protein
- protein protein
- genome wide
- physical activity
- amino acid
- weight loss
- randomized controlled trial
- cell death
- pregnant women
- mitochondrial dna
- intensive care unit
- systematic review
- high fat diet
- body mass index
- small molecule
- mechanical ventilation
- genome wide identification
- blood glucose
- blood pressure
- transcription factor
- insulin resistance
- glycemic control
- preterm birth
- extracorporeal membrane oxygenation
- genome wide analysis