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The molecular mechanism underlying hyperuricemia-induced lipid metabolism disorders is not clear. The purpose of the current study was to investigate the mechanism of lipid disturbances in a hyperuricemia mice model. RNA-Seq showed that differentially expressed genes (DEGs) in the fatty acid synthesis signaling pathway were mainly enriched and CXCL-13 was significantly enriched in protein-protein interaction networks. Western blotting, Q-PCR, and immunofluorescence results further showed that hyperuricemia upregulated CXCL-13 and disturbed lipid metabolism in vivo and in vitro. Furthermore, CXCL-13 alone also promoted the accumulation of lipid droplets and upregulated the expression of FAS and SREBP1, blocking AMPK signaling and activating the PKC and P38 signaling pathways. Silencing CXCL-13 reversed uric-acid-induced lipid droplet accumulation, which further downregulated FAS and SREBP1 expression, inhibited the p38 and PKC signaling, and activated AMPK signaling. In conclusion, hyperuricemia induces lipid metabolism disorders via the CXCL-13 pathway, making CXCL-13 a key regulatory factor linking hyperuricemia and lipid metabolism disorders. These results may provide novel insights for the treatment of hyperuricemia. NEW & NOTEWORTHY The underlying molecular mechanism of hyperuricemia-induced lipid metabolism disorders is still unclear. The study aimed to investigate the mechanism of lipid disturbance in hyperuricemia mice model. To our knowledge, we proposed for the first time that CXCL-13 may be a key regulator of hyperuricemia and lipid metabolism disorders. These results may provide new insights for the clinical treatment of hyperuricemia. [ABSTRACT FROM AUTHOR]

Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. The gut microbiota has been demonstrated to play significant roles in the immunity and metabolism of the host. In the present study, we constructed a hyperuricemic mouse model to investigate whether the metabolic disorder caused by hyperuricemia is related to intestinal dysbiosis. A significantly increased intestinal permeability was detected in hyperuricemic mice. The difference in microflora between wild-type and hyperuricemic mice accompanies the translocation of gut microbiota to the extraintestinal tissues. Such a process is followed by an increase in innate immune system activation. We observed increased LPS and TNF-α levels in the hyperuricemic mice, indicating that hyperuricemic mice were in a state of low-grade systemic inflammation. In addition, hyperuricemic mice presented early injury of parenteral tissue and disordered lipid metabolism. These findings suggest that intestinal dysbiosis due to an impaired intestinal barrier may be the key cause of metabolic disorders in hyperuricemic mice. Our findings should aid in paving a new way of preventing and treating hyperuricemia and its complications. NEW & NOTEWORTHY Hyperuricemia is associated with many metabolic diseases. However, the underlying mechanism remains unknown. We constructed a hyperuricemic mouse model to explore the relationship between intestinal dysbiosis and metabolic disorder caused by hyperuricemia. [ABSTRACT FROM AUTHOR]