Fuller 2020 J Appl Physiol (1985)
|Fuller KNZ, McCoin CS, Allen J, Bell-Glenn S, Koestler DC, Dorn Ii GW, Thyfault JP (2020) Sex and BNIP3 genotype, rather than acute lipid injection, modulate hepatic mitochondrial function and steatosis risk in mice. J Appl Physiol (1985) 128:1251-61.|
Abstract: Both lipid oversupply and poor mitochondrial function (low respiration and elevated H2O2 emission) have been implicated in the development of hepatic steatosis and liver injury. Mitophagy, the targeted degradation of low functioning mitochondria, is critical for maintaining mitochondrial quality control. Here, we used intralipid injections combined with acute (4day) and chronic (4-7wk) high-fat diets (HFD) to examine if hepatic mitochondrial respiration would decrease and H2O2 emission would increase with lipid overload. We tested these effects in male and female wild type (WT) mice and mice null for a critical mediator of mitophagy, BNIP3 (BNIP3 KO) housed at thermoneutral temperatures. Intralipid injection was successful in elevating serum triglycerides and NEFAs but had no impact on hepatic mitochondrial respiratory function or H2O2 emission. However, female mice had greater mitochondrial respiration on the acute HFD, lower H2O2 emission across both HFD durations, and were protected against hepatic steatosis. Unexpectedly, BNIP3 KO animals had greater hepatic mitochondrial respiration, better coupled respiration, and increased electron chain protein content after the 4day HFD compared to WT animals. Altogether, these data suggest that acute lipid overload delivered by a single intralipid bolus does not alter hepatic mitochondrial outcomes, but rather sex and genotype profoundly impact hepatic mitochondrial respiration and H2O2 emission.
Labels: MiParea: Respiration, Genetic knockout;overexpression, Gender, Exercise physiology;nutrition;life style
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k, O2k-Fluorometer