Scly, also known as selenocysteine β -lyase, is an intracellular enzyme crucial for selenium metabolism. It decomposes selenocysteine (Sec) into selenide and alanine, providing selenium for the synthesis of new selenoproteins [3,4]. Selenium is essential for proper brain function, energy metabolism regulation, and cellular function, and Scly is involved in the selenocysteine metabolism pathway, which is also related to ferroptosis prevention [1,2,3]. Genetic models, such as KO mouse models, have been valuable in studying its functions.

Whole-body knockout of Scly in mice increases susceptibility to metabolic syndrome and diet-induced obesity [2,3,5,6]. Mice lacking Scly exhibit hyperinsulinemia, hyperleptinemia, glucose intolerance, and hepatic steatosis [6]. Hypothalamic Agrp-specific Scly knockout in mice leads to reduced weight gain and adiposity on a high-fat diet, along with maintained leptin sensitivity [2]. Also, Scly disruption affects pyruvate levels and energy metabolism-related enzymes in the liver [5]. These KO mouse models reveal Scly's important role in energy homeostasis and metabolism-related diseases.

In conclusion, Scly plays a vital role in selenium recycling and metabolism, which is essential for maintaining normal physiological functions. The study of Scly KO mouse models has provided significant insights into its role in metabolic disorders such as obesity, hyperinsulinemia, and glucose intolerance, highlighting its potential as a target for treating metabolic diseases.