Guanidinoacetic acid (GAA) is a naturally occurring amino acid derivative that plays a critical role in energy metabolism. In recent years, a growing body of evidence has emerged supporting the importance of GAA in metabolic dysfunction. Hence, we aimed to investigate the effects of GAA on hepatic and adipose tissue metabolism, as well as systemic inflammatory responses in obese middle-aged mice models and attempted to explore the underlying mechanism. We found that dietary supplementation of GAA inhibited inguinal white adipose tissue (iWAT) hypertrophy in high-fat diet (HFD)-fed mice. In addition, GAA supplementation observably decreased the levels of some systemic inflammatory factors, including IL-4, TNF-α, IL-1β, and IL-6. Intriguingly, GAA supplementation ameliorated hepatic steatosis and lipid deposition in HFD-fed mice, which was revealed by decreased levels of TG, TC, LDL-C, PPARγ, SREBP-1c, FASN, ACC, FABP1, and APOB and increased levels of HDL-C in the liver. Moreover, GAA supplementation increased the expression of browning markers and mitochondrial-related genes in the iWAT. Further investigation showed that dietary GAA promoted the browning of the iWAT via activating the AMPK/Sirt1 signaling pathway and might be associated with futile creatine cycling in obese mice. These results indicate that GAA has the potential to be used as an effective ingredient in dietary interventions and thus may play an important role in ameliorating and preventing HFD-induced obesity and related metabolic diseases.

中文翻译：

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胍基乙酸可改善高脂饮食引起的肥胖中年小鼠的肝脏脂肪变性和炎症，并促进白色脂肪组织褐变

胍基乙酸 (GAA) 是一种天然存在的氨基酸衍生物，在能量代谢中发挥着关键作用。近年来，越来越多的证据支持 GAA 在代谢功能障碍中的重要性。因此，我们旨在研究GAA对肥胖中年小鼠模型的肝脏和脂肪组织代谢以及全身炎症反应的影响，并试图探索其潜在机制。我们发现，膳食补充 GAA 可抑制高脂饮食 (HFD) 喂养的小鼠腹股沟白色脂肪组织 (iWAT) 肥大。此外，补充 GAA 还可显着降低一些全身炎症因子的水平，包括 IL-4、TNF-α、IL-1β 和 IL-6。有趣的是，补充 GAA 可改善 HFD 喂养小鼠的肝脏脂肪变性和脂质沉积，这通过 TG、TC、LDL-C、PPARγ、SREBP-1c、 FASN、ACC、FABP1和APOB水平降低以及 HDL 水平升高来揭示。-C在肝脏中。此外，补充 GAA 还增加了 iWAT 中褐变标记物和线粒体相关基因的表达。进一步的研究表明，膳食 GAA通过激活 AMPK/Sirt1 信号通路促进 iWAT 褐变，并且可能与肥胖小鼠的无效肌酸循环有关。这些结果表明，GAA有潜力作为膳食干预中的有效成分，因此可能在改善和预防HFD引起的肥胖及相关代谢疾病方面发挥重要作用。