Tspo Depletion Exacerbates Steatosis Through Fatty Acid Uptake

Area of Science:

• Hepatology
• Molecular Biology
• Metabolic Diseases

Background:

• Translocator protein (TSPO) loss in vitro causes simple steatosis (SS).
• The in vivo role of TSPO in SS and MASLD remains unclear.
• Hypothesis: TSPO loss promotes early-stage MASLD.

Purpose of the Study:

• To investigate the in vivo effect of TSPO deficiency on simple steatosis.
• To elucidate the mechanisms by which TSPO impacts early-stage MASLD progression.

Main Methods:

• Utilized wild-type (WT) and TSPO knockout (KO) rats fed a NASH-inducing diet.
• Analyzed metabolic parameters, lipogenesis, fatty acid uptake, and mitochondrial function.
• Assessed protein expression (FASN, CD36, CPT1A, RAPTOR) and autophagy markers.

Main Results:

• TSPO KO rats exhibited increased insulin resistance, hypercholesterolemia, and hepatic steatosis.
• Enhanced de novo lipogenesis and free fatty acid uptake via CD36.
• Impaired mitochondrial function, elevated Acetyl-CoA, and suppressed autophagy.
• TSPO deficiency boosted fatty acid oxidation by increasing CPT1A expression.

Conclusions:

• TSPO deficiency exacerbates simple steatosis progression in early-stage MASLD.
• Mechanisms include enhanced CD36-mediated fatty acid uptake, elevated Acetyl-CoA, mitochondrial dysfunction, and impaired autophagy.
• TSPO plays a critical role in regulating hepatic lipid metabolism and mitochondrial function.