How Your Liver Handles Fat Is a Fine Balancing Act

Image created with Biorender. Credit: Rory Cunningham

Keeping a healthy amount of fat in your liver is simple on paper, but a little more complicated when you look under the metabolic hood. Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver injury that can range progressively from fat accumulation inside liver cells (steatosis), to fat buildup plus inflammation (steatohepatitis or NASH), to end-stage liver disease with sever scarring of liver (called cirrhosis), or to liver cancer. The further along you are in this spectrum of disease, the more difficult it is to reverse. Given that there are no approved therapies for end-stage liver disease, there is a lot of ongoing research to prevent or reverse initial NAFLD development and steatosis. 

Steatosis is a condition in which more than 5% of liver cells contain lipid (fat) droplets. It’s considered relatively benign in its early stages. You might wonder how lipids end up accumulating in the liver. To put it simply, fat accumulates in the liver when more lipids go into the cells than go out. To dive into this further, we need to know the different ways the liver handles its lipids. 

What Goes In …

Lipids can make their way into the liver in the form of free fatty acids that fat tissue releases into the bloodstream. Some of these fatty acids are taken up by the liver and are either used for energy immediately or are stored to be used later. The liver also imports lipids from the bloodstream that come from triglycerides in the food you eat. If you eat a meal containing fats, these will leave your small intestine and circulate around the body, with some ending up in the liver. 

The liver can also make its own lipids through a process called de novo lipogenesis. During this process, carbohydrates such as glucose and fructose are broken down and remade into free fatty acids. If the free fatty acids are not used for energy, they get stored as fat in the liver. People with NAFLD often have high circulating glucose and insulin levels in the bloodstream. These two conditions stimulate the de novo lipogenesis pathway, which means the livers of people with NAFLD make more fat naturally. 

… Also Comes Out

The liver cells’ mitochondria are where most of the lipids are burned for energy. During NAFLD development, mitochondrial function decreases, which reduces the ability of the liver to burn fats. The liver packages fat into lipoproteins that is secreted into the bloodstream. These lipoproteins are then absorbed by tissues throughout the body and the fat is either used for energy or stored for later use. Sending fat to other areas of the body helps regulate the amount of fat in the liver. 

You can help prevent the development of liver disease by maintaining a healthy body weight, not over-consuming calories and participating in regular physical activity. Exercise of any form can improve the liver mitochondria’s ability to burn fat and reduce de novo lipogenesis in the liver. Additionally, limiting your alcohol intake and eating a wide variety of fruits and vegetables will help protect the liver from toxins that can negatively affect its ability to handle lipids.

All these lifestyle factors influence the delicate fat balancing act played daily by the liver to maintain its important functions.

Rory Cunningham, PhD, is a former postdoctoral fellow at the National Cancer Institute and a scientist at the liver therapeutics company Ochre Bio. His research involves developing and phenotyping models of human liver perfusions.

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