# Lipophagy Dynamics in Hyperlipidemia Model ICR Mice Across Different High-Fat-Diet Feeding Durations

## TL;DR

This study examines how different durations of high-fat diets affect lipid metabolism and autophagy in mice, identifying a key time point for optimal modeling of hyperlipidemia.

## Contribution

The study identifies a specific time point (week 9) where autophagy and lipid metabolism show significant changes in HFD-induced hyperlipidemia in ICR mice.

## Key findings

- At week 9, P-AMPK/AMPK, P-mTOR/mTOR, and P-ULK1/ULK1 protein ratios were significantly reduced.
- LC3Ⅱ/LC3Ⅰ and P62 protein levels were notably elevated at week 9, indicating autophagy dysregulation.
- Week 9 marks a critical turning point in abdominal adipose metabolic disorder in HFD-fed ICR mice.

## Abstract

Hyperlipidemia (HLP) is a metabolic dysfunction marked by dysregulated lipid metabolism, which jeopardizes cardiovascular health. The function of autophagy modulated by the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in HLP pathogenesis has not been fully elucidated. Thus, this study centered on the impacts of different feeding durations on HLP models. ICR mice were given a high-fat diet (HFD) to induce the model, with durations set at 3, 6, 9, 12, and 15 weeks. Body weight, liver and adipose organ indices, serum and hepatic lipid levels, and pathological changes (assessed by Oil Red O and HE staining) were measured. Related pathway markers were detected via immunofluorescence, quantitative real-time PCR (qPCR), and Western blotting. At week 9, the relative protein expression ratios of P-AMPK/AMPK, P-mTOR/mTOR, and P-ULK1/ULK1 were markedly reduced, while the expression levels of LC3Ⅱ/LC3Ⅰ and P62 proteins were notably elevated, exhibiting transient dysregulation characteristics and suggesting a potential optimal modeling time point. It clarifies the temporal pattern, core molecular mechanism, and critical turning point of abdominal adipose metabolic disorder induced by a high-fat diet (HFD) in ICR mice. This study offers a credible basis for the optimal duration of HLP modeling and in vivo animal experimental design.