Role of srebps in the liver diseases

Azam Moslehi,1,* Zeinab hamidi-zad,2

1. Qom University of Medical Sciences
2. Qom University of Medical Sciences



Background and objectives: sterol regulator element binding proteins (srebps) are a family of transcription factors that involve in the biogenesis of cholesterol, fatty acids, and triglyceride. there are three members of srebps family: srebp-1a, srebp-1c and srebp-2. srebps regulate physiological functions of the many organs such as; thyroid, brain, heart, pancreas and hormone synthesis. beside of physiological effects, pathological circumstances; diabetes, endoplasmic reticulum stress, atherosclerosis and chronic kidney disease are associated with srebps expression changes.


Materials and methods: we studied 134 articles from pubmed and wed of science date bases.


Results: srebps involve in pathogenesis of the nonalcoholic fatty liver disease. it has been shown that srebp-1c binds to the patatin-like phospholipase3 (pnpla3) gene and activates its expression; pnpla3 then stimulates lipid accumulation in mice hepatocytes. overconsumption of fructose also stimulates srebp1c expression and leads to hepatic lipid accumulation. endoplasmic reticulum (er) stress induction increase srebp1c expression and other lipid metabolism related genes and provide hepatic steatosis and cirrhosis. in a study, we showed opioid receptor blockade attenuates er stress, decreases srebp expression and improves liver steatosis. liver steatosis is frequently found in the patients who are infected with hepatitis c virus2 (hcv). some studies have been shown that hcv non-structural protein 2 (ns2) and hcv nonstructural 4b (ns4b) protein increase srebps expression. moreover, srebps involve in pathogenesis of hepatocellular carcinoma (hcc). overexpression of srebp-1 is associated with large tumor size, high histological grade and advanced tumor-node-metastasis (tnm) stage in hcc patients.


Conclusion: srebps have a key role in pathogenesis of the nash, hepatitis and cancers. moreover, they provide lipid metabolism regulated cellular disorders in the hepatocyte that lead to steatosis and liver injury.


Srebp, liver, fatty acids, er stress