Oral Talks

2019 European Journal of Clinical Investigation  
Non-alcoholic fatty liver disease (NAFLD) is associated with high-caloric intake and physical inactivity. Among other pathological alterations, liver mitochondrialrelated dysfunction characterizes NAFLD development, but seems to be attenuated by physical exercise (PE). In addition to more prevalent metabolic conditions in which NAFLD is present, women with gestational diabetes mellitus (GDM) present signs of NAFLD. The aim of this study was to elucidate whether PE during pregnancy influences
more » ... er mitochondrial function in a GDM-associated NAFLD model. Methods: After 6 weeks under control (C) or high-fat-highsugar (HFHS) diets, female Sprague-Dawley rats were mated and distributed into the following experimental groups: C or HFHS; pregnant or non-pregnant; sedentary or exercised during pregnancy. Oral glucose tolerance test (OGTT) and histological analysis were used to confirm the presence of GDM and NAFLD, respectively. Liver mitochondrial function was assessed using complex I and II-related substrates. Results: Although body weight was not altered by HFHS or PE, gestational body weight gain was increased in sedentary HFHS group compared to C (~1.5-fold) or exercised HFHS groups (~1.3-fold). Pre-mating OGTT did not show difference between C and HFHS groups, while pregnant HFHSfed animals were more glucose intolerant, regardless of PE. Histological analysis confirmed the presence of steatosis in HFHS sedentary groups. Regarding liver mitochondrial function, pregnancy and HFHS per se negatively affected mitochondrial function, although the synergistic effect of both factors did not additionally deteriorate mitochondrial function. PE improved mitochondrial function of HFHS groups, regardless of pregnancy. Conclusion: Pregnancy and HFHS impaired mitochondrial function of sedentary rats. However, 3 weeks of PE during pregnancy was able to attenuate the effects of HFHS and/ or pregnancy on liver mitochondrial function on this animal model of NAFLD. ABSTRACTS (SOD1, SOD2) and SIRT3 were also analyzed. Compared to CSAA-fed WT mice, citrate synthase activity was slightly diminished at both 32 and 66 weeks of CDAA feeding. In addition, at 32 weeks, the CDAA diet resulted in significantly decreased enzymatic activities of MRC complex I, II, II+III and IV in WT mice compared to CSAA-fed animals. Strikingly, RIP3-/-mice showed an overall protection against CDAA-induced impairment of MCR complex activity, notably at 32 weeks. mRNA expression of PGC1α, NRF1 and TFAM was downregulated in CDAA-fed WT mice at both 32 and 66 weeks, but significantly increased in RIP3-/-mice. Similarly, SOD1, SOD2 and SIRT3 mRNA levels were downregulated in CDAA-fed WT mice, while RIP3 depletion significantly abrogated this effect at 32 weeks. In conclusion, impaired MRC complex activity correlates with inflammation, fibrosis and ROS overproduction in experimental NAFLD. RIP3 deficiency restores MRC complex activity, enhances mitochondrial biogenesis, increases ROS detoxification capacity and, collectively, halts NAFLD progression.
doi:10.1111/eci.13108 fatcat:i6bd4xxgvjc53lebt4ykh6ncuq