Sex and BNIP3 genotype, rather than acute lipid injection, modulate hepatic mitochondrial function and steatosis risk in mice
Kelly N. Z. Fuller, Colin S. McCoin, Julie Allen, Shelby Bell-Glenn, Devin C. Koestler, Gerald W. Dorn, John P. Thyfault
Abstract
This is the first study focusing on hepatic mitochondrial respiratory outcomes in response to lipid overload via a high-fat diet (HFD) combined with intralipid injection. Novel findings include no effect of intralipid injection on mitochondrial outcomes of interest, despite increased circulating lipid concentrations. However, we report pronounced differences in hepatic mitochondrial respiration, complex protein expression, and H 2 O 2 production by sex and BCL-2/adenovirus EIB 19-kDa interacting protein (BNIP3) genotype. Specifically, female mice had lower H 2 O 2 emission globally and on an acute HFD, females had greater hepatic mitochondrial respiration than males, whereas BNIP3 knockout (KO) animals had greater mitochondrial coupling and complex protein expression than wild-type (WT) animals.