Scientists discovered that a protein called FTO acts like a switch that controls how much fat builds up in the liver. When people eat too much fatty food, their bodies make too much FTO, which then tells the liver to store more fat. In this study, researchers used mice and human liver cells to show that blocking FTO reduced fat accumulation and improved liver health. This finding could lead to new treatments for fatty liver disease, a condition that affects millions of people worldwide and can cause serious health problems if left untreated.

The Quick Take

  • What they studied: How a protein called FTO controls whether the liver stores too much fat, and whether blocking this protein could prevent fatty liver disease
  • Who participated: Mice fed a high-fat diet to mimic human fatty liver disease, plus human liver cells grown in the laboratory treated with fatty acids
  • Key finding: When FTO was removed or reduced, liver cells accumulated significantly less fat and stayed healthier. FTO works by controlling another protein called HNF1A, which tells cells to make and store fat
  • What it means for you: This research suggests that drugs targeting FTO might help treat fatty liver disease, but these are early findings from lab and animal studies. Human clinical trials would be needed before any new treatment could be used in patients

The Research Details

Researchers used two main approaches to understand how FTO affects the liver. First, they created mice that ate a high-fat diet to develop fatty liver disease, similar to what happens in humans. They measured how much FTO was present in the liver tissue and tracked changes in fat buildup over time. Second, they used human liver cells grown in dishes and treated them with fatty acids to simulate the disease in a controlled laboratory setting. This allowed them to test what happened when they removed or reduced FTO in these cells.

The scientists used several advanced techniques to understand the mechanism. They performed co-immunoprecipitation, which is like a molecular detective game where they tracked which proteins interact with each other. They also used luciferase reporter assays, a method that uses a glowing protein to measure whether genes are turned on or off. These experiments helped them understand exactly how FTO controls other genes involved in fat storage.

Rescue experiments were a crucial part of the study. After showing that removing FTO helped, researchers added back the HNF1A protein to see if the benefits disappeared. This proved that FTO works specifically through HNF1A, not through some other pathway. They also examined human liver samples from patients with fatty liver disease to confirm their findings applied to real people.

This research approach is important because it moves from simple observations to understanding the actual mechanism—the ‘how’ and ‘why’ behind fatty liver disease. By using both animal models and human cells, the researchers could confirm their findings work in living systems and in human tissue. The rescue experiments were particularly valuable because they proved a cause-and-effect relationship, not just a correlation. This level of evidence is necessary before scientists can confidently propose FTO as a drug target.

Strengths of this study include the use of multiple experimental approaches that all pointed to the same conclusion, testing in both animal models and human cells, and the use of rescue experiments to prove cause-and-effect. The confirmation in human clinical samples adds real-world relevance. However, the study was conducted in laboratory and animal settings, not in living humans. The sample size for human samples was not specified in the abstract. Additionally, this is a single study, so the findings would benefit from being replicated by other research groups before being considered definitive.

What the Results Show

The main discovery was that FTO protein levels were significantly higher in mice with fatty liver disease compared to healthy mice. When researchers removed or reduced FTO in liver cells, fat accumulation dropped dramatically, and the cells were healthier and less likely to die. This suggested that FTO is a key driver of fatty liver disease.

The researchers then identified how FTO works: it controls another protein called HNF1A, which acts like a master switch for genes that make and store fat. Interestingly, FTO doesn’t work by changing the chemical structure of HNF1A’s genetic instructions (a process called m6A modification). Instead, FTO appears to control HNF1A through a different mechanism, which was a surprising finding.

When they looked at human liver samples from patients with fatty liver disease, they found that FTO levels were high while HNF1A levels were low—the opposite of what you’d want for a healthy liver. This confirmed that the FTO-HNF1A relationship they discovered in the lab actually occurs in real patients.

The most convincing evidence came from rescue experiments: when researchers added HNF1A back into cells where FTO had been removed, the protective effects disappeared and fat started accumulating again. This proved that FTO’s harmful effects depend entirely on controlling HNF1A.

Beyond the main findings, the study showed that blocking FTO also reduced oxidative stress (cellular damage from harmful molecules) and improved various blood markers related to liver and metabolic health in the mice. Cell survival improved when FTO was reduced, meaning fewer liver cells died. These secondary findings suggest that FTO affects liver health through multiple pathways, not just fat storage.

Previous research had identified FTO as important in metabolism and obesity, but this study is among the first to specifically explain how FTO drives fatty liver disease at the molecular level. Earlier work suggested FTO worked through m6A modifications (chemical tags on RNA), but this research shows that in the liver, FTO’s main effect on HNF1A doesn’t involve m6A changes. This finding refines our understanding and suggests that FTO may work differently in different tissues.

This study was conducted primarily in mice and human cells in dishes, not in living human patients. While the findings in human tissue samples are encouraging, they don’t prove that blocking FTO would safely treat fatty liver disease in people. The study didn’t test any actual drugs or treatments—only the removal of FTO itself. The exact sample size for human clinical samples wasn’t specified. Additionally, the study focused on one specific mechanism, and fatty liver disease is complex with many contributing factors. Long-term effects of blocking FTO weren’t examined, and potential side effects in other organs weren’t studied.

The Bottom Line

Based on this research, there is currently no recommendation for patients to change their behavior, as no human treatments have been tested yet. The findings suggest that FTO could be a promising drug target (moderate confidence level based on laboratory evidence). For people with fatty liver disease, the current evidence-based recommendations remain: maintain a healthy weight, eat a balanced diet low in processed foods and added sugars, exercise regularly, and limit alcohol. Anyone with fatty liver disease should work with their doctor on a personalized treatment plan.

This research is most relevant to people with metabolic dysfunction-associated steatotic liver disease (fatty liver disease), people at risk for developing it (those who are overweight, have diabetes, or eat a high-fat diet), and researchers developing new treatments. People without liver disease don’t need to change anything based on this study. This research is also important for pharmaceutical companies considering which proteins to target for new drug development.

If FTO-targeting drugs are developed, it would typically take 5-10 years of clinical trials before they could be available to patients. Even then, benefits would likely develop gradually over weeks to months of treatment, not immediately. This is a long-term research direction, not an immediate solution.

Want to Apply This Research?

  • Users with fatty liver disease could track liver health markers that might eventually be affected by FTO-targeting treatments: weekly weight, monthly blood work results (liver enzymes like ALT and AST, triglycerides, and blood sugar), and daily diet quality scores focusing on fat and sugar intake
  • While waiting for potential FTO-targeting drugs, users should focus on modifiable behaviors: reduce intake of high-fat and high-sugar foods, increase physical activity to at least 150 minutes per week, maintain a healthy weight, and limit alcohol. The app could send reminders for these evidence-based interventions and track progress
  • Set up monthly check-ins to review liver function blood tests with a healthcare provider, track weight trends over 3-month periods, monitor energy levels and symptoms, and maintain a food diary to identify patterns in diet quality. As new treatments emerge, the app could help track medication adherence and any changes in liver health markers

This research describes laboratory and animal studies investigating how a protein called FTO contributes to fatty liver disease. These findings have not yet been tested in human clinical trials, and no treatments based on this research are currently available for patients. This article is for educational purposes only and should not be considered medical advice. If you have fatty liver disease or are concerned about your liver health, please consult with your healthcare provider about appropriate screening, diagnosis, and treatment options. Do not make any changes to your current treatment plan based on this research. Always discuss new findings with your doctor before making health decisions.