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What Causes Fatty Liver Disease?

It has been shown that excessive intake of fat, cholesterol, and carbohydrates in the diet is correlated with the development of fatty liver disease. Scientists recently conducted a study to determine how each individual diet component affects the progression and initiation of fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a rising liver disease, currently affecting over 25% of the world’s population. NAFLD takes into account a broad range of pathologies, or stages, beginning with liver steatosis, an irregular accumulation of fats in liver cells, all the way up to hepatocellular carcinoma. The progression through the NAFLD stage has been hypothesized to require a multitude of different “stimulators” such as inflammation and oxidative stress. In line with this, both serum and liver levels of proinflammatory proteins known as tumor-necrosis factor alpha (TNF-α) and monocyte-chemoattractant protein-1 (MCP-1) show higher levels in patients with any range of NAFLD.

Both dietary fats and cholesterol are thought to be linked to the initiation and progression of fatty liver disease in humans and other animal models. Fructose could be another source of the development of fatty liver disease. The roles of fats, cholesterol, and carbohydrates remain unclear in the initiation and progression of fatty liver disease and more insight is necessary.

Is Fat or Fructose to Blame?

A research study in Denmark was recently published in the journal Diabetology& Metabolic Syndrome to compare the development of fatty liver disease through the effects of fat, fructose, and cholesterol in an animal model. The research team compared the effects of fat, fructose, and a combination of the two alongside increased cholesterol. They used 40 male rats which were randomly categorized into four different treatment groups: the control diet group, the high-fat diet group (HFD), the high-fructose diet (HFr) group, or a high-fat, high-fructose, and high-cholesterol diet (NASH) group. The rats were given the different diets for a period of 16 weeks. After the treatment period, the rats were collected and a liver histology was performed.

High Fat Diets Led to Fatty Liver Disease

The histology showed high-fat accumulation in the liver cells as well as inflammation in the rats that were given the NASH diet as well as the rats that were given the HFD diet alone. The changes in liver histology were not as prominent in the rats that were fed the HFr diet. As expected, the rats that were fed the NASH or HFD diets had increased amounts of triglycerides in their liver cells. The rats that were given the NASH diet had increased liver cholesterol levels. HFD and NASH fed rats both show a significant increase in MCP-1. HFD fed rats also show an increase in TNF-α as a mechanism for the development of fatty liver disease.

In conclusion, the scientists showed that dietary fat and cholesterol are the biggest stimulators of fatty liver initiation and development in rats. It also suggest that fructose most likely has repercussions on the lipid pool of the liver cells. Although these results are starting to piece together how fat, cholesterol, and carbohydrates play roles in the development of fatty liver disease, there are still many more questions to ask and mechanisms to asses.

Written by Ingrid Qemo, BSc

Reference: Jensen, V.S., et al. 2018. Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague-Dawley rats. DiabetolMetabSyndr. 10:4.



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