Stimulation of CT1 function

From Klotho protein to ammonia

Maintaining proper intracellular creatine content remains a vital challenge for various energy-demanding cells that heavily rely on creatine as a key high-energy phosphate-storage molecule. A highly-specialized creatine transporter (CT1) has been recognized as a cellular target for the fine-tuning of creatine homeostasis, with CT1 upregulation put forward as a novel therapeutic approach to stimulate creatine transfer across the cell membrane. In paper that has been just published in Frontiers in Nutrition, we explore several compounds that may activate CT1 upregulation and facilitate creatine uptake, and examine possible benefits and drawbacks of this approach in experimental and clinical nutrition. These include substrate availability, several protein kinases (including Klotho protein, mTOR, and SGK1), and hyperammonemia, with a number of pathways appears to be triggered by a caloric restriction or specific diet. Although preclinical studies reveal promising results, upregulating CT1 via dietary interventions requires a rather careful scrutinization in mechanistic tissue-specific clinical trials.