Induction of ileal permeability and alterations in metabolome in the gut–liver axis induced by 12α-hydroxylated bile acids in rats

概要

Hepatic steatosis
Non-alcoholic fatty liver disease (NAFLD) refers to a series of liver diseases that are
independent of alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to
non-alcoholic steatohepatitis (NASH). NAFL is defined as the presence of ≥ 5% hepatic
steatosis with or without mild inflammation and is slowly progressive (Chalasani et al.,
2018). NASH is characterized by the presence of hepatocellular injury in the form of
hepatocyte ballooning and is a more active form of the disease that can progress to
cirrhosis and fibrosis, and even liver cancer (Powell et al., 2021). Although less than
10% of NAFLD patients eventually develop liver cancer (Powell et al., 2021), there is
a large population of NAFLD. It is reported to affect about a quarter of the world's
population (Younossi et al., 2016). Also, NAFLD is closely linked to other metabolic
comorbidities such as obesity, diabetes mellitus, dyslipidemia, and hypertension
(Younossi et al., 2016). Thus, the prevalence of the disease is an increasing burden for
society. In 2020, an international expert group has put forward the concept of metabolic
dysfunction-associated fatty liver disease (MAFLD) to positively incorporate criteria
for diagnosis (Eslam et al., 2020; Fouad et al., 2020). The diagnosis of MAFLD is based
on the presence of steatosis together with one of the three metabolic risks, including
overweight/obesity, diabetes mellitus, and evidence of metabolic dysregulation (Eslam
et al., 2020).
A comprehensive understanding of the complex pathogenesis of MAFLD still
remains limited. The substrate overload may explain the metabolic mechanisms leading
to hepatic steatosis. Excess energy substrates (primarily carbohydrates and fatty acids)
are supplied to the liver, which exceeds the hepatic capacity to oxidize them to CO2 or
re-esterify to triglyceride (TG) and export as very-low-density lipoprotein (VLDL)
(Friedman et al., 2018). ...

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