Hepatic de novo lipogenesis (DNL) is a vital biosynthetic pathway within the liver, contributing to the lipids that are stockpiled and secreted by hepatocytes. This procedure is an extension of the compound metabolic networks at play within the liver, and is provided with substrate primarily through glycolysis and the metabolism of carbohydrates. A high‐carbohydrate diet can prime the DNL pathway with a large substrate load and increase rates of DNL. Outstandingly this leads to an amassing of DNL products, fatty acyl chains linked to coenzyme A, which can be incorporated into a plethora of lipid species. These lipids may perhaps then have further metabolic functions, which in turn may be toxic in cases of elevated DNL.

The role of DNL inside Non-alcoholic fatty liver disease (NAFLD) may substantiate a fruitful area of research. It appears to be a component of the pathological basis of the hugely prevalent NAFLD, which can be an imperative risk factor for Type 2 diabetes mellitus (T2DM).

It may be that DNL delivers a suitable pharmacological target for early interference to avert the onset of T2DM. This would prove immensely advantageous in the advanced world where the burdens of over‐nutrition are sustaining unparalleled increases in obesity, prediabetes and overt T2DM. It is clear that DNL is a contributor to the overall paradigm of these metabolic diseases. Investigators should consider the role of DNL as a part of the total pathogenic commotion that can lead to a failure of insulin secretion and signalling.

Source: Biol Rev Camb Philos Soc. 2016 May; 91(2): 452–468.