Hepatic senescence accompanies the development of NAFLD in non-aged mice independently of obesity
Legaki, A. I.
Papatheodoridi, A. M.
Pateras, I. S.
Gorgoulis, Vassilis G
AffiliationDepartment of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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AbstractSenescence 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 senescence is involved in the development of nonalcoholic fatty liver disease (NAFLD). However, previous studies have mainly focused on age-related senescence during NAFLD, in the presence or absence 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 senescence-associated genes and the presence of a robust hybrid histo-/immunochemical senescence-specific 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 senescence during steatosis development independently of obesity.
CitationMoustakas, II, Katsarou A, Legaki AI, Pyrina I, Ntostoglou K, Papatheodoridi AM, et al. Hepatic Senescence Accompanies the Development of NAFLD in Non-Aged Mice Independently of Obesity. Int J Mol Sci. 2021;22(7).
JournalInternational Journal of Molecular Sciences
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