Nuclear transcription factors affecting lipogenesis

Sterol regulatory element-binding protein 1 (SREBP-1) and related nuclear transcription factors are central regulators of the genes involved in lipogenesis. These factors, including SREBP-1, ChREBP, PPARγ, LXRα, USF1/2, and XBP1, respond to nutritional and hormonal signals—mainly glucose and insulin—to trigger the transcription of key lipogenic enzymes in liver and adipose tissue. SREBP-1 undergoes proteolytic activation, translocates to the nucleus, and binds sterol response elements in promoters of lipogenic genes to activate their transcription. PPARγ is a master regulator of adipogenesis and also impacts lipogenesis through direct transcriptional control. ChREBP is activated by glucose and regulates carbohydrate-induced lipogenic gene expression. LXRα, another nuclear hormone receptor, stimulates lipogenesis partly through transcriptional activation of SREBP-1c and ChREBP. Collectively, these transcription factors are critical for metabolic health, and their dysregulation is linked to obesity, fatty liver, and insulin resistance. Their manipulation by drugs represents both a promising therapeutic strategy and a source of potential side effects, making them important targets for metabolic disease intervention.

Other names

Sterol regulatory element-binding protein 1ADD1ChREBPUSF1PPARγLiver X receptor alphaXBP1SREBP-1aSREBP-1c

Agonism of nuclear hormone receptors (e.g., PPARγ, LXRα) to induce transcription factor activity; Inhibition of proteolytic activation or nuclear translocation of SREBP-1; Modulation of chromatin remodeling and histone acetylation (epigenetic mechanisms)