TY - JOUR
TI - Hepatic senescence accompanies the development of NAFLD in non-aged mice independently of obesity
AU - Moustakas, I.I.
AU - Katsarou, A.
AU - Legaki, A.-I.
AU - Pyrina, I.
AU - Ntostoglou, K.
AU - Papatheodoridi, A.-M.
AU - Gercken, B.
AU - Pateras, I.S.
AU - Gorgoulis, V.G.
AU - Koutsilieris, M.
AU - Chavakis, T.
AU - Chatzigeorgiou, A.
JO - International Journal of Molecular Sciences
PY - 2021
VL - 22
TODO - 7
SP - null
PB - MDPI AG
SN - 1422-0067
TODO - 10.3390/ijms22073446
TODO - malonaldehyde;  messenger RNA;  messenger RNA, adult;  animal experiment;  animal model;  Article;  cell aging;  controlled study;  disease course;  DNA methylation;  female;  gene expression;  immunohistochemistry;  liver cell;  liver fatty degeneration;  male;  mouse;  nonalcoholic fatty liver;  nonhuman;  obesity;  oxidative stress;  steatosis;  telomere length;  upregulation;  young adult;  animal;  C57BL mouse;  insulin resistance;  lipid diet;  lipid peroxidation;  liver;  liver cell;  metabolism;  nonalcoholic fatty liver;  obesity;  pathology;  telomere;  ultrastructure, Animals;  Cellular Senescence;  Diet, High-Fat;  DNA Methylation;  Female;  Hepatocytes;  Insulin Resistance;  Lipid Peroxidation;  Liver;  Male;  Mice;  Mice, Inbred C57BL;  Non-alcoholic Fatty Liver Disease;  Obesity;  Oxidative Stress;  RNA, Messenger;  Telomere
TODO - Senescence is considered to be a cardinal player in several chronic inflammatory and metabolic pathologies. The two dominant mechanisms of senescence include replicative senescence, predominantly depending on age-induced telomere shortening, and stress-induced senescence, triggered by external or intracellular harmful stimuli. Recent data indicate that hepatocyte senes-cence is involved in the development of nonalcoholic fatty liver disease (NAFLD). However, previ-ous studies have mainly focused on age-related senescence during NAFLD, in the presence or ab-sence of obesity, while information about whether the phenomenon is characterized by replicative or stress-induced senescence, especially in non-aged organisms, is scarce. Herein, we subjected young mice to two different diet-induced NAFLD models which differed in the presence of obesity. In both models, liver fat accumulation and increased hepatic mRNA expression of steatosis-related genes were accompanied by hepatic senescence, indicated by the increased expression of senes-cence-associated genes and the presence of a robust hybrid histo-/immunochemical senescence-spe-cific staining in the liver. Surprisingly, telomere length and global DNA methylation did not differ between the steatotic and the control livers, while malondialdehyde, a marker of oxidative stress, was upregulated in the mouse NAFLD livers. These findings suggest that senescence accompanies NAFLD emergence, even in non-aged organisms, and highlight the role of stress-induced senes-cence during steatosis development independently of obesity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
ER -