Fatty liver disease is rising as a global health concern. Often considered a 'silent' disease as it shows few or no symptoms, fatty liver disease, however, can get serious, depending on its cause and progression. A new study has found that a certain hormone can reverse fatty liver disease.
A groundbreaking study by the researchers at the University of Oklahoma found that a hormone can reverse the effects of fatty liver disease in mice. The study is published in Cell Metabolism.
What is fatty liver disease?
Fatty liver, medically known as hepatic steatosis, is a condition in which fat builds up in the liver. There are two major types of fatty liver disease: alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). AFLD, as the name suggests, occurs in people who drink large amounts of alcohol. NAFLD, on the other hand, affects people who drink little or no alcohol. Though the cause of nonalcoholic fatty liver disease (NAFLD) is unknown, people who have type 2 diabetes, or prediabetes, obesity, are middle-aged or older, have high blood pressure, are prone to the disease.
How does the hormone control fatty liver disease?
The researchers found that the hormone FGF21 (fibroblast growth factor 21) can reverse fatty liver disease. The hormone works primarily by signaling the brain to improve liver function. They delved into how FGF21 acts on the brain to influence liver metabolism. Understanding the mechanism of action of the hormone could become instrumental as a target for a new class of highly anticipated drugs that are in Phase 3 clinical trials.
“Fatty liver disease, or MASLD (metabolic dysfunction-associated steatotic liver disease), is a buildup of fat in the liver. It can progress to MASH (metabolic dysfunction-associated steatohepatitis) during which fibrosis and, ultimately, cirrhosis can occur. MASLD is becoming a very big problem in the United States, affecting 40% of people worldwide, and there is currently only one treatment approved by the Food and Drug Administration to treat MASH. A new class of drugs, based on FGF21 signaling, is showing good therapeutic benefits in clinical trials, but until now, the mechanism for how they work has been unclear,” Matthew Potthoff, Ph.D., the lead author and a professor of biochemistry and physiology at the University of Oklahoma College of Medicine and deputy director of OU Health Harold Hamm Diabetes Center said in a statement.
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The findings showed that FGF21 was effective at causing signaling in the model species that changed the liver’s metabolism. The researchers found that this process lowered the liver’s fat, and the fibrosis too was reversed. The hormone also sent a separate signal directly to the liver, specifically to lower cholesterol.
“It’s a feedback loop where the hormone sends a signal to the brain, and the brain changes nerve activity to the liver to protect it. The majority of the effect comes from the signal to the brain as opposed to signaling the liver directly, but together, the two signals are powerful in their ability to regulate the different types of lipids in the liver,” Potthoff added.
Similar to the GLP-1s (glucagon-like peptide 1) weightloss drugs that regulate blood sugar levels and appetite, FGF21 acts on the brain to regulate metabolism. Interestingly, both are hormones produced from peripheral tissues: GLP-1 from the intestine and FGF21 from the liver, and both work by sending a signal to the brain.
“It is interesting that this metabolic hormone/drug works primarily by signaling to the brain instead of to the liver directly, in this case. FGF21 is quite powerful because it not only led to a reduction of fat, but it also mediated the reversal of fibrosis, which is the pathological part of the disease, and it did so while the mice were still eating a diet that would cause the disease. Now, we not only understand how the hormone works, but it may guide us in creating even more targeted therapies in the future,” the lead author added.
A groundbreaking study by the researchers at the University of Oklahoma found that a hormone can reverse the effects of fatty liver disease in mice. The study is published in Cell Metabolism.
What is fatty liver disease?
Fatty liver, medically known as hepatic steatosis, is a condition in which fat builds up in the liver. There are two major types of fatty liver disease: alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). AFLD, as the name suggests, occurs in people who drink large amounts of alcohol. NAFLD, on the other hand, affects people who drink little or no alcohol. Though the cause of nonalcoholic fatty liver disease (NAFLD) is unknown, people who have type 2 diabetes, or prediabetes, obesity, are middle-aged or older, have high blood pressure, are prone to the disease.
How does the hormone control fatty liver disease?
The researchers found that the hormone FGF21 (fibroblast growth factor 21) can reverse fatty liver disease. The hormone works primarily by signaling the brain to improve liver function. They delved into how FGF21 acts on the brain to influence liver metabolism. Understanding the mechanism of action of the hormone could become instrumental as a target for a new class of highly anticipated drugs that are in Phase 3 clinical trials.
“Fatty liver disease, or MASLD (metabolic dysfunction-associated steatotic liver disease), is a buildup of fat in the liver. It can progress to MASH (metabolic dysfunction-associated steatohepatitis) during which fibrosis and, ultimately, cirrhosis can occur. MASLD is becoming a very big problem in the United States, affecting 40% of people worldwide, and there is currently only one treatment approved by the Food and Drug Administration to treat MASH. A new class of drugs, based on FGF21 signaling, is showing good therapeutic benefits in clinical trials, but until now, the mechanism for how they work has been unclear,” Matthew Potthoff, Ph.D., the lead author and a professor of biochemistry and physiology at the University of Oklahoma College of Medicine and deputy director of OU Health Harold Hamm Diabetes Center said in a statement.
Video
The findings showed that FGF21 was effective at causing signaling in the model species that changed the liver’s metabolism. The researchers found that this process lowered the liver’s fat, and the fibrosis too was reversed. The hormone also sent a separate signal directly to the liver, specifically to lower cholesterol.
“It’s a feedback loop where the hormone sends a signal to the brain, and the brain changes nerve activity to the liver to protect it. The majority of the effect comes from the signal to the brain as opposed to signaling the liver directly, but together, the two signals are powerful in their ability to regulate the different types of lipids in the liver,” Potthoff added.
Similar to the GLP-1s (glucagon-like peptide 1) weightloss drugs that regulate blood sugar levels and appetite, FGF21 acts on the brain to regulate metabolism. Interestingly, both are hormones produced from peripheral tissues: GLP-1 from the intestine and FGF21 from the liver, and both work by sending a signal to the brain.
“It is interesting that this metabolic hormone/drug works primarily by signaling to the brain instead of to the liver directly, in this case. FGF21 is quite powerful because it not only led to a reduction of fat, but it also mediated the reversal of fibrosis, which is the pathological part of the disease, and it did so while the mice were still eating a diet that would cause the disease. Now, we not only understand how the hormone works, but it may guide us in creating even more targeted therapies in the future,” the lead author added.
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