Fgf21, or Fibroblast growth factor 21, is a peptide hormone synthesized by multiple organs. It regulates energy homeostasis through a heterodimeric receptor complex with FGF receptor 1 (FGFR1) and β -klotho, playing crucial roles in glucose and lipid metabolism, energy balance, and has anti-inflammatory properties [1,2]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In KO mouse models, adiponectin knockout mice were refractory to several therapeutic benefits of FGF21, such as alleviation of obesity-associated hyperglycemia, hypertriglyceridemia, insulin resistance, and hepatic steatosis. This indicates adiponectin mediates FGF21 actions on energy metabolism and insulin sensitivity [5]. In kidney-specific fgf21-deficient mice, aged or obese conditions exacerbated autophagy stagnation due to severer lysosomal overburden, suggesting FGF21 protects against chronic kidney disease progression by alleviating autophagy stagnation [3].

In conclusion, Fgf21 is essential for regulating energy and macronutrient metabolism, and has anti-inflammatory and organ-protective functions. Mouse KO/CKO models have revealed its roles in obesity-related metabolic diseases, chronic kidney disease, and non-alcoholic steatohepatitis, providing insights into its potential as a therapeutic target for these diseases [1,2,3,4].