The role of SIRT4 in obesity: from molecular mechanisms to clinical implications

Obesity has emerged as a pervasive global public health issue, and the etiology of obesity is now understood to be increasingly intricate and multifactorial, encompassing genetic predispositions, sedentary lifestyles coupled with excessive caloric intake, as well as environmental and social interactions. Recent studies have indicated a close association between SIRT4 and obesity. The pathophysiological mechanisms underlying its influence on obesity predominantly involve four interconnected pathways: fatty acid oxidation, adipocyte differentiation, insulin secretion, and inflammation. Furthermore, emerging studies are exploring the clinical translational potential of SIRT4. As a mitochondria-localized member of the sirtuin family, SIRT4 possesses both deacetylase and ADP-ribosyltransferase enzymatic activities. This mitochondrial enzyme is involved in metabolic regulation through modulating energy homeostasis and lipid metabolic processes, inflammatory signaling pathways, neuroendocrine regulatory networks, and the epigenetics of adipocyte differentiation. However, the lack of comprehensive synthesis and critical evaluation of existing evidence has left the precise relationship between SIRT4 and obesity incompletely understood. Therefore, this review systematically synthesizes current knowledge regarding SIRT4's mechanistic involvement in obesity development, while evaluating clinical correlations and regulatory strategies. This review focuses on the potential of SIRT4 in the regulation of obesity and the progress in related studies. The search criteria encompass keywords related to the role of SIRT4 in physiological and biochemical processes such as lipid and energy metabolism, adipocyte differentiation, as well as its clinical applications, with a total of 63 references cited.