Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia

• DOI: 10.1172/jci.insight.173240
• Publication Date: 2024-07-07T18:00:27Z
• Authors: Yiheng Huang; Liujun Chen; Lisha Li; Yadan Qi; Haibin Tong; Hong Wu; Jinjie Xu; Lin Leng; Sukhinder Cheema; Guang Sun; Zhengyuan Xia; John McGuire; Brian Rodrigues; Lawrence H. Young; Richard Bucala; Dake Qi
• Keywords: Hypertriglyceridemia; Male; Mice, Knockout; Adipose Tissue, White; Palmitic Acid; Down-Regulation; Middle Aged; Mice, Inbred C57BL; Lipoprotein Lipase; Mice; Adipocytes; Animals; Humans; Receptor, PAR-2; Female; Obesity; Macrophage Migration-Inhibitory Factors; Triglycerides; Research Article

Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating LPL its relationship with development of hypertriglyceridemia are largely unknown. WAT from obese humans exhibited high PAR2 expression, which was inversely correlated gene. Decreased expression also elevated plasma TG levels, suggesting that might regulate by downregulating LPL. In mice, aging palmitic acid diet (PD) increased WAT, associated a level macrophage migration inhibitory factor (MIF). MIF downregulated activity adipocytes binding CXCR2/4 receptors inhibiting Akt phosphorylation. overexpression model, high-circulating levels suppressed LPL, this suppression TGs but not FA. Following PD feeding, were significantly reduced, reduction reversed Par2-/- mice. Recombinant infusion restored decreased attenuated adipocyte storage, leading to hypertriglyceridemia. These data collectively suggest downregulation PAR2/MIF may contribute