Combined Cold Exposure and Exercise Improves NAFLD: Mechanistic Insights

Area of Science:

• Metabolic disease research
• Exercise physiology
• Environmental adaptation

Background:

• Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population, posing a significant health risk.
• Current treatments for NAFLD are limited, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the effects of combined cold exposure and exercise on NAFLD in a mouse model.
• To elucidate the molecular mechanisms underlying the therapeutic potential of this combined intervention.

Main Methods:

• A high-fat diet-induced NAFLD mouse model was used.
• Mice were subjected to cold exposure, exercise, or a combination for 8 weeks.
• Intervention efficacy was assessed via body/liver weight, blood lipids, FGF21 levels, and liver histopathology.
• Key protein and gene expression (FGF21, β-klotho, FGFR1) was analyzed to explore molecular pathways.

Main Results:

• Combined cold exposure and exercise significantly reduced body weight, liver weight, and liver/body weight ratio compared to single interventions.
• Blood lipids, circulating FGF21, and liver glycogen levels were significantly decreased.
• Liver fat deposition and fibrosis were reduced, with increased FGFR1 and β-klotho protein expression, indicating FGF21 pathway activation.

Conclusions:

• Combined cold exposure and exercise synergistically alleviate NAFLD progression in mice.
• The FGF21-β-klotho/FGFR1 pathway activation enhances lipid metabolism and reduces liver injury.
• This dual intervention shows translational potential for non-pharmacological NAFLD therapies.