Hepatic lipogenesis and related metabolic gene expression (DNL)

Hepatic lipogenesis and related metabolic gene expression refers to the complex biochemical pathway of de novo lipogenesis (DNL) and the regulatory network that controls the synthesis of fatty acids within the liver [Diabetes Journals, 2020; NIH, 2020]. This process is primarily driven by the conversion of excess dietary carbohydrates into fatty acids, which are subsequently incorporated into triglycerides for storage or export [NIH, 2020]. The pathway is tightly regulated at the transcriptional level by master regulators such as Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) and Carbohydrate-Responsive Element-Binding Protein (ChREBP), which respond to insulin and glucose signals [Diabetes Journals, 2020; NIH, 2020]. These transcription factors induce the expression of key enzymes, including Acetyl-CoA Carboxylase (ACC), Fatty Acid Synthase (FASN), and Stearoyl-CoA Desaturase 1 (SCD1) [Diabetes Journals, 2020]. Pathological upregulation of hepatic lipogenesis is a central feature of metabolic-associated steatotic liver disease (MASLD) and non-alcoholic steatohepatitis (NASH), contributing to hepatic fat accumulation and lipotoxicity [Spandidos Publications, 2020; NIH, 2020]. Therapeutic strategies aim to reduce liver fat by inhibiting these lipogenic enzymes or by activating nuclear receptors like the Farnesoid X Receptor (FXR) to downregulate the lipogenic gene program [NIH, 2020; Life Science Alliance, 2021]. While effective at reducing liver fat, these therapies must balance efficacy with potential systemic metabolic side effects such as changes in plasma lipid profiles or dermatological issues [NIH, 2020].

Other names

De novo lipogenesisHepatic fatty acid synthesisLipogenic gene expressionDNL pathway

Inhibition of rate-limiting enzymes (ACC, FASN, SCD1, ACLY) or modulation of transcription factors (FXR, LXR, SREBP-1c) to suppress the de novo synthesis of fatty acids and triglycerides in the liver.