α1-acid Glycoprotein mitigates MASLD progression by modulating liver and adipose tissue function

Area of Science:

• Hepatology
• Metabolic Diseases
• Biochemistry

Background:

• Hepatokine dysregulation is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD).
• Alpha-1-acid glycoprotein (AGP), a hepatokine, is investigated for its role in MASLD progression.

Purpose of the Study:

• To investigate the role of AGP in MASLD progression.
• To evaluate AGP's therapeutic potential for MASLD.

Main Methods:

• Analysis of hepatic RNA-seq datasets from MASLD patients.
• Utilized a high-fat diet (HFD)-induced mouse model of MASLD.
• Employed AGP-knockout (AGP-KO) mice and exogenous human AGP (hAGP) administration.

Main Results:

• Hepatic AGP gene expression decreased with MASLD progression.
• AGP-KO mice on HFD showed exacerbated steatosis, obesity, inflammation, and impaired glucose tolerance.
• hAGP protected against lipotoxicity and attenuated MASLD progression in mice by reducing mitochondrial dysfunction and adipose tissue inflammation.

Conclusions:

• Reduced endogenous AGP levels may drive MASLD progression.
• AGP demonstrates potential as a novel therapeutic agent for MASLD, targeting both liver and adipose tissue.