The Proteomic Analysis of Intermittent Fasting Alone or with GLP-1RA in NAFLD Rats

Area of Science:

• Hepatology
• Metabolic Diseases
• Pharmacology

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a growing health concern.
• Intermittent fasting (IF) and glucagon-like peptide-1 receptor agonists (GLP-1RA) show promise for NAFLD treatment.
• This study investigates the combined effects of alternate-day fasting (ADF) and liraglutide on NAFLD.

Purpose of the Study:

• To evaluate the efficacy of ADF alone versus ADF combined with liraglutide (A+L) in a rat model of NAFLD.
• To explore the underlying molecular mechanisms influenced by these therapeutic interventions.
• To identify potential new therapeutic targets for NAFLD management.

Main Methods:

• A NAFLD rat model was established using a high-fat diet.
• Rats were treated with ADF, A+L, or served as controls for 5 weeks.
• Evaluations included liver morphology, body weight, serum lipids, insulin sensitivity, and liver proteomics.

Main Results:

• ADF alone reduced body weight, food intake, lipids, ALT, and improved NAFLD scores.
• A+L demonstrated superior reductions in body weight, food intake, triglycerides, and LDL compared to ADF alone.
• Proteomic analysis revealed upregulation of GPR39 and Tmem41b, and downregulation of HSD17B2 in A+L treated rats.

Conclusions:

• Combined ADF and liraglutide therapy significantly enhances metabolic health and NAFLD amelioration in obese rats.
• This synergistic approach suggests potential for improved clinical outcomes in NAFLD patients.
• The identified molecular targets warrant further investigation for novel NAFLD therapies.