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Studies on the development of novel non-alcoholic steatohepatitis (NASH) models using rats

Saigo, Yasuka 京都大学 DOI:10.14989/doctor.k24651

2023.03.23

概要

NAFLD is a chronic liver disease, which has been diagnosed in an increasing number
of patients worldwide. NAFLD is a continuum of non-alcoholic liver dysfunction ranging
from simple steatosis to NASH, and some of them progress to cirrhosis and liver cancer
[33]. The majority of NAFLD patients have obesity, type 2 diabetes, and dyslipidemia;
multiple factors (genetic, environmental, and epigenetic) are thought to influence disease
development and progression, unlike in viral hepatitis and autoimmune liver diseases [34].
In recent years, in addition to these factors, age and sex differences have been considered
factors responsible for the development of NAFLD. The prevalence and incidence of
NAFLD tends to be higher in men than in premenopausal women (or those younger than
50–60 years), and higher in postmenopausal women (or those older than 50–60 years)
[35]. This difference in the incidence and prevalence of NAFLD based on sex and age
might be because of the presence of male hormones or female hormonal changes due to
menopause. In fact, in young women with NAFLD, higher testosterone levels are
associated with a higher risk of NASH and NASH-induced liver fibrosis, as well as a high
risk of abdominal fat [36]. Furthermore, menopause is associated with changes in body
composition, specifically with increased levels of intra-abdominal fat and increased waist
circumference corrected for BMI, both of which are linked to an increased risk of
metabolic diseases, including type 2 diabetes [37]. In vitro studies using human
hepatocytes have shown that 17-β-estradiol inhibits cell death, mitochondrial dysfunction,
and triglyceride accumulation under NAFLD-like conditions, suggesting that it has
hepatoprotective effects [38]. ...

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