Qiu Yu, Li Cantao, Hua Ying, Huang Yan, Zhang Lu, Xu Jiaman, Zheng Junna, Fu Zhiling, Zhang Xiaoxi, Li Fenfen, Xia Daozong
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Int J Obes (Lond). 2025 Aug 7. doi: 10.1038/s41366-025-01875-6.
Growing evidence has indicated an association between obesity, measured by body mass index (BMI), and urate levels, as well as the risk of gout. However, BMI inadequately reflects the body's fat distribution, including variations in gluteofemoral, abdominal subcutaneous, and visceral adipose tissue (GFAT, ASAT, and VAT). This study aimed to utilize Mendelian randomization (MR) to investigate the causal associations between genetically predicted fat distribution, urate levels, and the risk of gout.
We performed a comprehensive investigation of nine fat distribution traits, including raw and adjusted measures of GFAT, ASAT, VAT, and their corresponding ratios, as potential exposures. Using two-sample MR analysis, we investigated the causal associations between these fat distribution traits, urate levels, and gout risk. Additionally, we conducted multivariate MR analysis to assess whether the interaction between different fat depots influenced causal effects. Furthermore, we applied a two-step MR analysis to assess their mediating effects on gout risk through urate levels. We also conducted multiple sensitivity analyses to confirm the robustness and validity of our results.
The MR analysis revealed a significant negative causal association between GFAT (both raw and adjusted) and urate levels as well as gout risk. Conversely, a significant positive causal association was observed between ASAT and urate levels. The mediation analysis revealed that 36% and 40% of the protective effect of raw and adjusted GFAT on the risk of gout was mediated by urate level, respectively. These findings remained consistent across multivariable analyses.
This study provides preliminary evidence supporting the association between fat distribution, urate levels, and gout risk, suggesting a potential lower risk of gout in individuals with a pear-shaped body.
越来越多的证据表明，以体重指数（BMI）衡量的肥胖与尿酸水平以及痛风风险之间存在关联。然而，BMI 并不能充分反映身体的脂肪分布，包括臀股部、腹部皮下和内脏脂肪组织（GFAT、ASAT 和 VAT）的变化。本研究旨在利用孟德尔随机化（MR）来研究基因预测的脂肪分布、尿酸水平和痛风风险之间的因果关系。
我们对九个脂肪分布特征进行了全面研究，包括 GFAT、ASAT、VAT 的原始和调整测量值及其相应比例，作为潜在暴露因素。使用两样本 MR 分析，我们研究了这些脂肪分布特征、尿酸水平和痛风风险之间的因果关系。此外，我们进行了多变量 MR 分析，以评估不同脂肪库之间的相互作用是否影响因果效应。此外，我们应用两步 MR 分析来评估它们通过尿酸水平对痛风风险的中介作用。我们还进行了多次敏感性分析，以确认结果的稳健性和有效性。
MR 分析显示，GFAT（原始和调整后）与尿酸水平以及痛风风险之间存在显著的负因果关系。相反，观察到 ASAT 与尿酸水平之间存在显著的正因果关系。中介分析显示，原始和调整后的 GFAT 对痛风风险的保护作用分别有 36%和 40%是由尿酸水平介导的。这些发现在多变量分析中保持一致。
本研究提供了初步证据，支持脂肪分布、尿酸水平和痛风风险之间的关联，表明梨形身材个体患痛风的风险可能较低。
