Saturated fatty acid‐enriched diet exacerbate hepatic mitochondrial dysfunction in rats subjected to maternal protein restriction

Abstract

The nutritional transition that the western population has undergone is increasingly associated with chronic metabolic diseases. In this context, dietary factors has been linked to oxidative stress, making the body vulnerable to mitochondrial dysfunction and reactive oxygen species. In this work, we evaluated the impact of a saturated fatty acid‐enriched diet in the post‐weaning offspring subjected to maternal protein restriction on the liver mitochondrial bioenergetics. Wistar rats were mated and during gestation and lactation, mothers received control diets (NP, normal protein content 17%) or low protein (LP, 8% protein). After weaning, rats received either NL (normolipidic) or HL (+59% SFA) diets up to 90 days of life. It was verified that all respiratory states of hepatic mitochondria showed a reduction in the LP group subjected to the post‐weaning HL diet (LP‐HL), basal state (−43.7%), state 3 (−37.3%), state 4 (−32.1%) and uncoupled state (−60.4%). Similarly, respiratory control was significantly lower (p<0.01). This group also presented greater mitochondrial swelling compared to controls (p<0.01), potentiated after Ca2+ addition (p <0,01) and prevented in the presence of EGTA (calcium chelator) (p<0.001); and cyclosporin A (mitochondrial permeability transition pore inhibitor) (p<0.0001). These effects were associated to increased liver protein and lipid peroxidation and reduced anti‐oxidant enzymes activities in the LP group fed HL diet after weaning. Additionaly, it was observed increase in PGC‐1α and VDAC and decrease in Tfam gene expressions compared to LP‐NL (p<0.05). Our data suggest that SFA‐enriched HFD induces mitochondrial dysfunction associated with oxidative stress, greater expression of VDAC that may potentiate the opening of the mitochondrial permeability transition pore, and lower mitochondrial biogenesis in the liver of adults rats, with major effects in animals previously submitted to maternal protein restriction.Support or Funding InformationThis study was supported by FACEPE (Brazil), CNPq (Brazil) and CAPES/COFECUB (Brazil/France).