Remund Nicole P, Larsen John G, Shin Marley J, Warren Cali E, Palmer Isabelle L, Kim Iris J, Cooper-Leavitt Elijah T, Clarke Derek M, Beus Colson G, Johnson Richard J, Arroyo Juan A, Reynolds Paul R, Bikman Benjamin T
Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Metabolites. 2024 Dec 4;14(12):679. doi: 10.3390/metabo14120679.
Uric acid (UA), a metabolite of purine and fructose metabolism, is linked to inflammation and metabolic disorders, including gout and cardiovascular disease. Its pro-inflammatory effects are largely driven by the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to increased cytokine production. Beta-hydroxybutyrate (BHB), a ketone produced during fasting or carbohydrate restriction, has been shown to reduce inflammation. This study explores the role of BHB in mitigating the inflammatory and metabolic effects of elevated uric acid levels. We utilized a murine muscle cell culture treated with UA and BHB. Muscle cells treated with UA had increased production of pro-inflammatory cytokines and reduced cell viability. Co-treatment with BHB reversed these effects, improving cell survival and reducing cytokine levels. Additionally, uric acid impaired mitochondrial function and increased oxidative stress, which were mitigated by BHB. Furthermore, uric acid disrupted insulin signaling, but BHB co-treatment restored insulin sensitivity. These findings suggest that BHB holds therapeutic potential by counteracting the inflammatory and metabolic disruptions caused by elevated uric acid, making it a promising target for conditions such as hyperuricemia and metabolic syndrome.
尿酸（UA）是嘌呤和果糖代谢的一种代谢产物，与炎症和代谢紊乱有关，包括痛风和心血管疾病。其促炎作用主要由含pyrin结构域的核苷酸结合寡聚化结构域样受体家族3（NLRP3）炎性小体的激活驱动，导致细胞因子产生增加。β-羟基丁酸（BHB）是禁食或碳水化合物限制期间产生的一种酮体，已被证明可减轻炎症。本研究探讨了BHB在减轻尿酸水平升高的炎症和代谢影响中的作用。我们利用了用UA和BHB处理的小鼠肌肉细胞培养物。用UA处理的肌肉细胞促炎细胞因子产生增加，细胞活力降低。与BHB共同处理可逆转这些作用，提高细胞存活率并降低细胞因子水平。此外，尿酸损害线粒体功能并增加氧化应激，而BHB可减轻这些情况。此外，尿酸会破坏胰岛素信号传导，但BHB共同处理可恢复胰岛素敏感性。这些发现表明，BHB通过抵消尿酸升高引起的炎症和代谢紊乱而具有治疗潜力，使其成为高尿酸血症和代谢综合征等病症的有希望的靶点。
