HuR promotes triglyceride synthesis and intestinal fat absorption

Area of Science:

• Molecular Biology
• Gastroenterology
• Metabolic Diseases

Background:

• Triacylglyceride (TAG) synthesis in the small intestine is key for dietary fat absorption.
• The precise molecular mechanisms regulating TAG synthesis require further investigation.

Purpose of the Study:

• To elucidate the role of the RNA-binding protein HuR (ELAVL1) in regulating TAG synthesis and dietary fat absorption.
• To investigate the impact of HuR on high-fat-diet-induced metabolic disorders.

Main Methods:

• Investigated HuR's association with Dgat2 mRNA and Mgat2 pre-mRNA.
• Utilized intestinal epithelium-specific HuR knockout mouse models.
• Assessed dietary fat absorption, TAG synthesis, and metabolic parameters.

Main Results:

• HuR binds to Dgat2 mRNA 3' UTR, stabilizing it, and to Mgat2 pre-mRNA intron 1, promoting its processing.
• Intestinal HuR deficiency reduces DGAT2 and MGAT2 expression.
• Reduced fat absorption and mitigation of high-fat-diet-induced obesity and NAFLD were observed in HuR knockout models.

Conclusions:

• HuR plays a critical role in promoting dietary fat absorption by regulating TAG synthesis in the small intestine.
• Targeting HuR may offer a therapeutic strategy for managing obesity and non-alcoholic fatty liver disease (NAFLD).