*Geek Box: Liver Fat

*Geek Box: Pathways of Hepatic Fat

 How does fat get into the liver? There are a number of origins of hepatic fat, and the respective contributions of different sources can differ whether we are looking at the fed vs. fasted state, or healthy individual’s vs. individuals with obesity or non-alcoholic fatty liver disease [NAFLD].

In the fasted state, the primary source of fatty acids delivered to the liver is from breakdown of stored fats [adipose tissue lipolysis]. In the fed state, dietary fats [triglycerides] and carbohydrate are absorbed through the small intestine. Dietary fats are packaged into chylomicrons and transported to body tissues. As the triglycerides are broken down, chylomicron remnants are formed, which are taken up by the liver: these account for about 24% of dietary triglycerides. In addition, fatty acids which “spillover” from chylomicrons are also taken up by the liver. Thus, dietary fat absorbed has two pathways to the liver: as chylomicron remnants or spillover fatty acids.

In the fed state, the majority of liver fatty acids [45-75%] remain from systemic circulation taken up by the liver. The carbohydrate taken in through diet may be converted to fat through a process known as ‘de novo lipogenesis’. However, the contribution of DNL is not as high as previously thought; in healthy individuals DNL may only contribute <5% of fatty acids delivered to the liver, while in individuals with NAFLD this can be up to 22-24%.

There is also the splanchnic pathway, which if you haven’t heard the term before, ‘splanchnic’ refers to visceral abdominal depots. ‘Splanchnic lipolysis’ thus describes the breakdown and release of fatty acids from visceral fat depots, and this is highly relevant for liver fat as the hepatic portal vein provides a rapid means of uptake for splanchnic fat. In healthy individuals in a fasted state, splanchnic lipolysis may account for between 5% and 10% of liver fatty acids, however, in individuals with high levels of visceral fat this may be up to 30%. Thus, there are multiple pathways through which the liver may accumulate fat, and the primary sources relate to fat metabolism and dietary intake, rather than the conversion of carbohydrate.