Postprandial Triglyceride-Rich Lipoproteins-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Inflammation in White Adipocytes

Abstract

Background: Obesity and postprandial hypertriglyceridemia, characterized by an increase in triglyceride-rich lipoproteins (TRLs), cause chronic low-grade inflammation. It is unclear how postprandial TRLs affect inflammation in white adipocytes.

Objectives: The objectives of the study were to explore the inflammatory response of postprandial TRLs in white adipocytes and investigate the possible mechanism.

Methods: We measured postprandial triglyceride (TG) and high-sensitivity C-reactive protein (hsCRP) concentrations in 204 recruited subjects and treated white adipocytes from mice with postprandial TRLs from above patients with hypertriglyceridemia.

Results: Serum hsCRP concentrations and BMI were positively related to TG concentrations in the postprandial state. Postprandial TRLs increased mRNA and protein expression of inflammatory factors, including interleukin-1β, via the NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway, and impaired autophagy flux in white adipocytes of mice. TRLs also induced lysosomal damage as evidenced by the reduced protein expression of lysosome-associated membrane proteins-1 and Cathepsin L. Inhibition of Cathepsin B, NLRP3, and mTOR signaling improved autophagy/lysosome dysfunction and inhibited the activation of the NLRP3/Caspase-1 pathway and inflammatory factors induced by TRLs in white adipocytes.

Conclusions: Our results suggest that postprandial hypertriglyceridemia causes chronic inflammation in adipocytes through TRL-induced lysosomal dysfunction and impaired autophagic flux in an mTOR-dependent manner.

Keywords: adipocytes; autophagy; inflammasome; obesity; triglyceride-rich lipoproteins.