Cartilage Intermediate Layer Protein 2 Aggravates Hepatic Lipid Accumulation and Inflammation Through the IRE1α/XBP1...

Area of Science:

• Hepatology
• Molecular Biology
• Metabolic Diseases

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition characterized by liver fat accumulation.
• Endoplasmic reticulum (ER) stress and inflammation are key contributors to MASLD pathogenesis.
• The specific role of CILP2 in MASLD has not been fully elucidated.

Purpose of the Study:

• To investigate the role of CILP2 in the development and progression of MASLD.
• To explore the underlying molecular mechanisms by which CILP2 influences hepatic lipid metabolism and inflammation.

Main Methods:

• Hepatic steatosis was induced in mice using a high-fat diet.
• CILP2 was overexpressed or knocked out (KO) in mouse livers and hepatocytes.
• Gene expression analysis, lipid content measurement, and inflammatory cytokine assessment were performed.

Main Results:

• CILP2 expression was elevated in steatotic livers and hepatocytes.
• CILP2 overexpression increased fatty acid synthesis, lipid accumulation, and pro-inflammatory cytokine expression.
• CILP2 knockout attenuated high-fat diet-induced steatosis and improved glucose metabolism.
• CILP2 activated the IRE1α/XBP1 ER stress pathway, promoting lipid synthesis and inflammation.

Conclusions:

• CILP2 exacerbates hepatic lipid accumulation and inflammation in MASLD through the IRE1α/XBP1 pathway.
• Targeting CILP2 may offer a novel therapeutic strategy for MASLD intervention.