Hyperuricemia induces lipid disturbances mediated by LPCAT3 upregulation in the liver

Abstract

Potential underlying molecular mechanisms for uric acid‐induced lipid metabolic disturbances had not been elucidated clearly. This study investigated the effects and underlying mechanisms of uric acid on the development of lipid metabolic disorders. We collected blood samples from 100 healthy people and 100 patients with hyperuricemia for whom serum lipid analysis was performed. Meanwhile, a mouse model of hyperuricemia was generated, and lipidomics was performed on liver tissues, comparing control and hyperuricemia groups, to analyze lipid profiles and key metabolic enzymes. Uric acid directly induced serum lipid metabolic disorders in both humans and mice based on triglycerides, total cholesterol, and low‐density lipoprotein cholesterol. Through lipidomic analysis, 46 lipids were differentially expressed in hyperuricemic mouse livers, and the phosphatidylcholine composition was altered, which was mediated by LPCAT3 upregulation. High‐uric acid levels‐induced p‐STAT3 inhibition and SREBP‐1c activation in vivo and in vitro. Moreover, LPCAT3‐knockdown significantly attenuated uric acid‐induced p‐STAT3 inhibition, SREBP‐1c activation, and lipid metabolic disorders in L02 cells. In conclusion, uric acid induces lipid metabolic disturbances through LPCAT3‐mediated p‐STAT3 inhibition and SREBP‐1c activation. LPCAT3 could be a key regulatory factor linking hyperuricemia and lipid metabolic disorders. These results might provide novel insights into the clinical treatment of hyperuricemia.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

“…The synthesis of TG will need NADPH and produce uric acid [32], the increase of serum uric acid provides raw materials for TG synthesis, HUA maybe a causal factor for high TG, and the lipidomics result was consistent with the literature reports [33,34]. acyltransferase activity and catalyzes the production of PCs [36], so the levels of PC and LPC were both up-regulated in HUA rats. PE is an early indicators for the risk of atherogenesis [37], and high serum UA levels have an independent association with increased arterial stiffness [38] Plantaginis semen significantly inhibited the expression of URAT1 in the renal tissue of HUA rats, indicating that Plantaginis semen could achieve the effect of treating HUA by promoting uric acid excretion.…”

Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

“…LPCs are biosynthesized from PCs through glycerophospholipid metabolism, this process is catalyzed by cytoplasmic phospholipase A2 (PLA2) and can be activated by UA [ 55 ]. UA can activate the phospholipid-remodeling enzymes LPCAT3 in vivo and in vitro, and LPCAT3 possesses primary LPC acyltransferase activity and catalyzes the production of PCs [ 56 ]. The enhancement of PLA2 and LPCAT3 activity results in accelerated glycerophospholipid metabolism, so the levels of PC and LPC were both up-regulated in HUA rats.…”

The Role of Apoptosis Pathway in the Cytotoxicity Induced by Fresh and Aged Zinc Oxide Nanoparticles

“…After quantification, reverse transcription was performed using TransGene RT-PCR kit (TransGene Biotech, Beijing, China) to obtain cDNA from the RNA template according to the manufacturer’s protocols. The resulting cDNA samples were quantified by using the Q5000 UV–Vis Spectrophotometer and then analyzed using SYBR-Green as fluorescence dye (TransGene Biotech, Beijing, China) on Roche RT-PCR system (Applied Biosystems) [ 25 ].…”