Sterol Regulatory Element-Binding Proteins and Metabolic Diseases: Mechanisms, Implications, and Therapeutic Strategies

Metabolic diseases, including obesity, diabetes, and cardiovascular disorders, are increasingly prevalent due to genetic, environmental, and lifestyle factors. Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that regulate genes involved in lipid synthesis and cholesterol homeostasis. Dysregulation of SREBPs contributes to metabolic disorders, with overactivation of SREBP-1c driving excessive lipid synthesis, leading to hyperlipidemia. In diabetes, altered SREBP activity impairs insulin secretion and promotes lipid accumulation, exacerbating disease progression. SREBP-2 is critical for cholesterol metabolism and is linked to atherosclerosis. This review explores the therapeutic potential of targeting SREBPs. Compounds such as betulin, fatostatin, xanthohumol, vitamin D derivatives, and BF175 can modulate SREBP activity, reduce lipid accumulation, and improve metabolic outcomes in experimental models. Clarifying SREBP regulatory mechanisms across tissues, advancing small-molecule modulators, and applying gene-editing technologies such as CRISPR-Cas9 may enable more personalized therapeutic strategies. Integrating lifestyle interventions with pharmacological treatments may offer a comprehensive approach to improving therapeutic outcomes in metabolic diseases.