Advances of GADD45b in hepatic glucose and lipid metabolism

Growth arrest and DNA damage-inducible 45b (GADD45b) was initially discovered to be involved in processes such as cell cycle arrest, differentiation and apoptosis. It is an important signal regulatory molecule in cells, responsible for signal transduction under various physiological or environmental stimuli. The GADD45b gene belongs to the GADD45 gene family. This gene is commonly expressed in human and fetal tissues, but the expression is tissue-specific, with high expression in the liver and bone marrow. The GADD45b protein is a small, evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus. Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3, and it has functions including improving tissue fibrosis and inflammation progression, inhibiting cell autophagy, and enhancing neural function recovery. GADD45b plays a significant role in tumors, innate immunity, neurological diseases, and disorders of hepatic glucose and lipid metabolism. The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year in China and has become a serious public health issue in the country. Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD. Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders. Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes, and enhance the expression of PGC1a, thereby promoting hepatic gluconeogenesis. Additionally, GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein. Therefore, the roles of GADD45b in promoting hepatic gluconeogenesis, inhibiting fatty acid transport, and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases. This paper reviews the characteristics and functions of the GADD45b protein, as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases, aiming to provide reference for further GADD45b research.