Metabolic dysfunction–associated steatotic
liver disease (MASLD), previously known as non-
alcoholic fatty liver disease (NAFLD) is the most common
liver disease with a worldwide
prevalence estimated at 30% of the general
population. To better understand the influence of MASLD progression on cardiovascular
disease, the aim of the study was to develop a new physiopathological mouse model able to develop progressive MASLD, along with atherosclerosis development, in a reasonable period of time. LDLr - / - mice were crossed with PPARα-deficient mice in order to obtain LDLr- / - mice expressing (LDLr - / - PPARα + / +) or not (LDLr - / - PPARα - / -) PPARα. Female mice were challenged with a high-
fat diet during 12 and 18 weeks. Histological liver analysis showed that, compared to control diet, LDLr - / - PPARα + / + mice under
high fat diet developed mostly
steatosis at 12 weeks, and then exhibited all characteristics of human MASLD, namely the
steatosis,
inflammation and ballooning-triad, with presence of
fibrosis at 18 weeks. This MASLD progression over time in LDLr - / - PPARα + / + was aggravated in LDLr - / - PPARα + / + mice. The present invenion defines a new relevant mouse model of progressive MASLD, developing all the characteristics of human MASLD (
steatosis,
inflammation, ballooning,
fibrosis), in a relatively short time period (12-18 weeks), along with simultaneous atherosclerosis development.