De novo lipogenesis (DNL) is a metabolic process in which the body produces new fatty acids from non-fat sources, such as carbohydrates, protein, and alcohol. This process primarily occurs in the liver and adipose (fat) tissues, and is regulated by several enzymes and hormones.

During DNL, the body converts excess dietary carbohydrates and protein into fatty acids through a series of biochemical reactions. The first step of DNL is the conversion of glucose into acetyl-CoA through a process called glycolysis. Acetyl-CoA is then converted into malonyl-CoA by the enzyme acetyl-CoA carboxylase (ACC). Malonyl-CoA is used as a substrate by the fatty acid synthase (FAS) complex to synthesize fatty acids, which are then incorporated into triglycerides and stored in adipose tissue or used as an energy source.

DNL is regulated by several hormones, including insulin, glucagon, and leptin. Insulin promotes DNL by stimulating the uptake of glucose and amino acids, and activating ACC and FAS enzymes. Conversely, glucagon and leptin inhibit DNL by inhibiting ACC and FAS enzymes and promoting the breakdown of stored fats.

Although DNL is an important metabolic process, excessive DNL can lead to the accumulation of fat in the liver and contribute to the development of metabolic diseases such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD).
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