Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

Azienda Ospedaliero Universitaria Santa Maria della Misericordia Dip Anatomia e Patologia Udine Italy

Department of Biological and Medical Sciences Faculty of Pharmacy in Hradec Kralove Charles University Prague Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

Department of Medical Sciences University of Trieste Trieste Italy

Fondazione Italiana Fegato AREA science Park Trieste Italy

IRCCS Ospedale Burlo Garofolo Pediatric Hospital Clinical Chemistry Laboratory Trieste Italy

Medical Research Institute AREA science Park Trieste Italy

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