SREBPs: regulators of cholesterol/lipids as therapeutic targets in metabolic disorders, cancers and viral diseases

Abstract

SREBPs control genes involved in cholesterol/lipid metabolism, membrane synthesis and fat storage. Aberrant SREBP activities have been linked to conditions associated with metabolic syndrome, including insulin resistance, obesity, elevated circulating LDL-C and triglycerides, and nonalcoholic fatty liver diseases. In addition, SREBPs have been implicated in cancer cell proliferation and enveloped viral replication through regulation of membrane synthesis. Therapeutic approaches to block SREBP functions linked to disease states may act through potentiation of SREBP negative regulators such as AMP-activated kinase or the sirtuin, SIRT1, or by inhibiting the proteolytic maturation into the active transcription factor forms. Additionally, cofunctional miRNAs embedded within the SREBP genomic loci (miR-33a/b) may also serve as novel therapeutic targets to ameliorate cardiometabolic diseases. Taken together, aberrant SREBP-linked activities could represent important targets of therapies to limit lipid/cholesterol synthesis or membrane production in metabolic diseases, cancer progression and viral pathogenesis.

Keywords::

• AMPK
• cholesterol membrane production
• lipid
• metabolic syndrome
• miR-33a/b
• mTOR
• SREBP