Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction

Area of Science:

• Biochemistry
• Cell Biology
• Metabolic Disorders

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern.
• The ketogenic diet (KD) shows promise as a lifestyle intervention for MASLD management.

Purpose of the Study:

• To investigate the effects of KD on metabolic parameters in a mouse model of MASLD.
• To elucidate the underlying mechanisms, particularly focusing on mitochondrial dynamics and function.

Main Methods:

• High-fat diet (HFD)-induced MASLD mice were treated with KD for two weeks.
• Assessed liver fat, ALT, AST, and hepatic mitochondrial dynamics (electron microscopy, Western blot).
• Evaluated mitochondrial function (qPCR, ATP content) and lipid deposition in vitro using HepG2 cells.

Main Results:

• KD partially improved the MASLD phenotype, reducing hepatic fat and liver enzymes.
• KD normalized mitochondrial dynamics by decreasing Fis1 and Drp1 levels.
• KD ameliorated mitochondrial dysfunction, increasing ATP levels and fatty acid oxidation genes.

Conclusions:

• A 2-week KD partially alleviates lipid deposition and improves mitochondrial dynamics and function in MASLD mouse livers.
• The ketone body β-hydroxybutyric acid (β-OHB) plays a role in mitigating mitochondrial dysfunction and lipid accumulation.