Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies

Metabolism-related diseases, including diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease, are becoming increasingly prevalent, thereby posing significant threats to human health and longevity. Proteins, as the primary mediators of biological activities, undergo various posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, methylation, and SUMOylation, among others, which substantially diversify their functions. These modifications are crucial in the physiological and pathological processes associated with metabolic disorders. Despite advancements in the field, there remains a deficiency in contemporary summaries addressing how these modifications influence processes of metabolic disease. This review aims to systematically elucidate the mechanisms through which PTM of proteins impact the progression of metabolic diseases, including diabetes, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Additionally, the limitations of the current body of research are critically assessed. Leveraging PTMs of proteins provides novel insights and therapeutic targets for the prevention and treatment of metabolic disorders. Numerous drugs designed to target these modifications are currently in preclinical or clinical trials. This review also provides a comprehensive summary. By elucidating the intricate interplay between PTMs and metabolic pathways, this study advances understanding of the molecular mechanisms underlying metabolic dysfunction, thereby facilitating the development of more precise and effective disease management strategies. Posttranslational modifications of proteins are involved in the development of metabolism-related diseases such as diabetes mellitus, obesity, hyperlipidemia, and nonalcoholic fatty liver disease. PTMs mediates the development of diabetes mellitus by affecting insulin homeostasis, glucose metabolism, diabetic complications, gluconeogenesis, and beta-cell function. PTMs is involved in obesity by affecting autophagy, FA metabolism, lipid accumulation, and insulin resistance. PTM influences cholesterol metabolism, FA metabolism, and lipid accumulation in the development of hyperlipidemia. PTMs is involved in the development of NAFLD by affecting FA oxidation, autophagy, lactate accumulation, insulin signaling pathway and inflammation. image