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 bisphosphatase domain. TIGAR mainly functions as a fructose-2,6-bisphosphatase, hydrolyzing fructose-1,6-diphosphate and fructose-2,6-diphosphate to inhibit glycolysis. By doing so, it facilitates the pentose phosphate pathway, producing NADPH and ribose, reducing intracellular reactive oxygen species (ROS), maintaining energy metabolism balance, regulating autophagy and stem cell differentiation, and promoting cell survival. It also has non-enzymatic functions, interacting with multiple proteins to mediate various cellular processes [2].

In murine models, ablation of myeloid Tigar attenuated sepsis-induced inflammation, indicating that macrophage TIGAR promotes inflammation by directly binding to TAK1 and enhancing its ubiquitination and auto-phosphorylation [1]. In TIGAR transgenic mice, an increase in fat mass and a trend towards an obesity phenotype were observed. TIGAR overexpression in adipocytes increased LRRK2 levels, suppressing macroautophagy and chaperone-mediated autophagy and increasing lipid accumulation. Fat-specific TIGAR knockdown alleviated obesity symptoms [3].

In conclusion, TIGAR plays crucial roles in multiple biological processes such as energy metabolism, autophagy, and redox balance. Studies using gene-knockout (KO) or conditional-knockout (CKO) mouse models have revealed its significance in diseases like sepsis and obesity, providing insights into potential therapeutic targets for these conditions.