Progress in animal models for studying hyperuricemia.

Area of Science:

• Biochemistry
• Metabolic Disorders
• Animal Models

Background:

• Hyperuricemia (HUA) is a common metabolic disorder caused by abnormal purine metabolism and poor urate excretion.
• Effective animal models are essential for understanding HUA pathophysiology and developing new treatments.

Purpose of the Study:

• To systematically review and evaluate various chemically induced, gene-edited, environmental, exercise, and microbiota-based HUA models.
• To highlight the strengths and limitations of each model in simulating human uric acid handling.
• To propose a standardized framework for evaluating HUA models to advance translational research.

Main Methods:

• Systematic review of existing literature on HUA animal models.
• Analysis of models across species including rodents, poultry, primates, zebrafish, and silkworms.
• Evaluation of model utility in validating existing therapies and identifying novel therapeutic targets.

Main Results:

• Various HUA models have been identified, each with unique advantages and disadvantages for studying human uric acid metabolism.
• These models have successfully validated standard treatments like xanthine oxidase inhibitors and uricosurics.
• Emerging therapeutic targets, including the gut-NLRP3 inflammasome axis and SIRT1-mediated ABCG2 regulation, have been uncovered.

Conclusions:

• A unified three-tier framework based on biochemical, mechanistic, and pathological criteria is proposed for standardizing HUA model evaluation.
• This framework will aid in selecting appropriate models and accelerating the translation of research findings into clinical applications for hyperuricemia.
• Standardized models are crucial for advancing the development of effective therapies for hyperuricemia.