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Exosomes from Short-Term High-Fat or High-Sucrose Fed Mice Induce Hepatic Steatosis through Different Pathways
Carlos Castaño1,2, Anna Novials1,2, Marcelina Párrizas2
1Pathogenesis and Prevention of Diabetes Group, Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Cells
|January 8, 2023
Summary
Short-term high-fat diets cause obesity and fatty liver disease by promoting lipid storage, while high-sucrose diets induce liver changes first. Exosomes from these diets altered gene expression, identifying miR-22-3p as a potential biomarker for metabolic-associated fatty liver disease (MAFLD) patients.
Area of Science:
- Metabolic diseases
- Molecular biology
- Nutritional science
Background:
- Obesity, metabolic-associated fatty liver disease (MAFLD), and type 2 diabetes share common metabolic phenotypes but distinct causes.
- Understanding early metabolic dysfunction is crucial for disease prevention and management.
Purpose of the Study:
- To compare the initial metabolic alterations induced by short-term high-fat (HFD) versus high-sucrose (SAC) diets.
- To investigate the role of plasma exosomal microRNAs (miRNAs) in diet-induced metabolic changes.
- To identify potential circulating biomarkers for MAFLD.
Main Methods:
- Utilized animal models fed short-term HFD or SAC diets.
- Employed transcriptomic, metabolic, and calorimetric analyses.
- Analyzed plasma exosomal miRNA profiles and performed exosome injection experiments.
Main Results:
- HFD rapidly induced obesity and hepatic steatosis via lipid accumulation.
- SAC promoted gluconeogenesis and de novo lipogenesis, leading to hepatic steatosis before obesity.
- Distinct plasma exosomal miRNA profiles were observed between HFD and SAC groups; exosome transfer partially mimicked donor phenotypes.
- Identified circulating miR-22-3p as a potential biomarker for MAFLD patient stratification.
Conclusions:
- Dietary fat and sugar differentially impact adipose and hepatic metabolism, influencing exosomal miRNA profiles.
- Exosomal miRNAs play a role in mediating diet-induced metabolic adaptations.
- Circulating miR-22-3p shows promise as a biomarker for stratifying MAFLD patients.
