Hepatic mitochondrial bioenergetic and dynamic behaviour adaptations in response to high-fat feeding

Introduction: High-fat feeding induces hepatic lipid accumulation associated with concomitant mitochondrial fat oxidation enhancement and electron-chain impairment that result in excessive formation of reactive oxygen species. Little is known about hepatic mitochondrial dynamic behaviours adaptation to high-fat feeding. Mitochondria are dynamic organelles that frequently undergo fission and fusion processes, imbalances in which have recently emerged as important etiological factors in obesity and insulin-resistance. Bearing in mind that fish-oil feeding has anti-steatotic effects, the present work aimed to evaluate the effects of high-lard (mainly saturated fatty acids) and high-fish-oil (mainly omega-3 polyunsaturated fatty acids) diets on both hepatic mitochondrial bioenergetic and dynamic behaviour. Methods: Hepatic lipid accumulation was monitored in rats fed a high-lard or high-fish-oil (40% J/J) diet for 6 weeks. Mitochondrial functions were assessed by evaluating FADH2 linked respiratory rates, fatty acid oxidation rates, energetic efficiency (by measuring basal and fatty acid induced proton leak kinetics), and oxidative stress (by measuring H2O2 release and aconitase activity). Mitochondrial dynamics behaviour was assessed by analysing the proteins relevant to the processes of fusion (MFN2, OPA1) and fission (DRP1, Fis1) (by western blot and immunohistochemical analysis). Results: Hepatic lipid accumulation, electron chain impairment and oxidative stress induced by high-lard diet were associated with both decreased fatty acid induced proton leak and a shift toward mitochondrial fission processes (decreased MFN2 content and increased DRP1 and Fis1 content). On the other hand, the anti-steatotic effect of high-fish oil feeding was associated with mild uncoupling (increases in both basal and fatty acid induced proton leak kinetics), oxidative stress prevention and increased mitochondrial fusion processes. Conclusions: Fission phenotype and increased energetic efficiency are associated with the steatotic effect of high-lard diet, whereas fusion phenotype and decreased energetic efficiency contributed to the anti-steatotic effect of high-fish oil diet.