TIGAR, short for TP53-induced glycolysis and apoptosis regulator, is a downstream target gene of p53. It contains a sequence similar to the 6-phosphofructose kinase/fructose-2,6-bisphosphatase domain. TIGAR mainly functions as a fructose-2,6-bisphosphatase to inhibit glycolysis, promoting the pentose phosphate pathway to produce NADPH and ribose. This helps maintain energy metabolism balance, regulate autophagy, and promote cell survival. It also has non-enzymatic functions, interacting with multiple proteins to mediate cell cycle arrest, inflammatory response, etc. Genetic models, such as KO or CKO mouse models, are valuable for studying its functions [4].

In a murine sepsis model, ablation of myeloid Tigar attenuated sepsis via inflammation inhibition, indicating that macrophage TIGAR promotes inflammation by directly binding to TAK1 and promoting its ubiquitination and auto-phosphorylation [2]. In obese TIGAR transgenic mice, TIGAR exacerbates obesity by triggering LRRK2-mediated defects in macroautophagy and chaperone-mediated autophagy in adipocytes, while fat-specific TIGAR knockdown alleviates obesity symptoms [3]. In colorectal cancer cells, knockdown of TIGAR increased erastin-induced ferroptosis, suggesting TIGAR induces ferroptosis resistance via the ROS/AMPK/SCD1 pathway [1].

In conclusion, TIGAR plays essential roles in energy metabolism, autophagy, and cell survival. Studies using TIGAR KO/CKO mouse models have revealed its significance in diseases like sepsis, obesity, and colorectal cancer. Understanding TIGAR's functions provides potential therapeutic targets for these disease areas.