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 to inhibit glycolysis, facilitating the pentose phosphate pathway to produce NADPH and ribose. This helps maintain energy metabolism balance, regulate autophagy and stem cell differentiation, and promote cell survival. It is also involved in various biological processes such as anti-oxidative stress, reducing inflammation, and inhibiting apoptosis [3,4].

In murine sepsis models, myeloid Tigar ablation attenuated sepsis-induced inflammation as TIGAR directly binds to TAK1 and promotes its ubiquitination and auto-phosphorylation, highlighting its role in macrophage-orchestrated inflammation [1]. In obese TIGAR transgenic mice, TIGAR exacerbates obesity by triggering LRRK2-mediated defects in macroautophagy and chaperone-mediated autophagy in adipocytes, suggesting its role in lipid metabolism [2]. In gestational diabetes mellitus models, loss of TIGAR in trophoblast cells increased ROS, driving a phenotypic switch and pyroptosis through the NLRP3-ASC-caspase-1 signaling pathway [5].

In conclusion, TIGAR plays essential roles in multiple biological processes including energy metabolism, inflammation, autophagy, and lipid metabolism. Studies using gene knockout or conditional knockout mouse models have revealed its significance in diseases such as sepsis, obesity, and gestational diabetes mellitus, providing potential therapeutic targets for these conditions.