December 22, 2018
2 min read

Researchers use FGF21 hormone for understanding liver disease, obesity, diabetes

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The hormone fibroblast growth factor 21, or FGF21, can be used as a biomarker for hepatic mitochondrial stress in methylmalonic acidemia as well as a potential tool for better understanding fatty liver disease, obesity and diabetes, according to a study from the National Human Genome Research Institute.

Charles P. Venditti, MD, PhD, a senior investigator in the institute’s medical genomics and metabolic genetics branch, and colleagues have been researching methylmalonic acidemia (MMA), an inborn error of metabolism, since 2003. In this study, the researchers were assessing potential markers that could be used to measure mitochondrial dysfunction in the liver using a mouse model. The researchers were able to recreate a “metabolic crisis” like those experienced by people with methylmalonic acidemia in mice using a fasting challenge. From this experiment, they found that FGF21 was “extremely elevated” in mice with liver disease.

“Our findings improve our understanding of what defines the metabolic stress adaptation response in MMA and should help to better predict who is at risk to develop the life-threatening metabolic crises that occur in these patients,” Venditti told Endocrine Today. “FGF21 levels may also serve as a highly correlated biomarker as the testing of new genomic therapies (AAV, mRNA) that are targeted to the liver enter the clinic. Understanding the role of FGF21 in MMA might also shed new light on common disorders, such as fatty liver disease, obesity and diabetes, because of the different ways vitamin B12 metabolism and MMA affect mitochondrial function.”

Although the process of going from trials in mice to human health care is usually elongated, Venditti and colleagues said they believe that this finding can already be utilized in clinical practice, specifically as it relates to liver and kidney transplantation. For people with MMA, liver transplants are not a cure for the condition, but they can help alleviate symptoms by adding a missing enzyme. In addition, because most patients with MMA are projected to experience terminal stages of renal failure, kidney transplantation is often required. According to Venditti, this new biomarker will enable physicians to better select patients for such procedures as well as predict the development of severe complications.

“This work can be immediately translated for the clinical care of MMA patients,” Venditti told Endocrine Today. “Medical teams can use FGF21 levels to predict who among their MMA patients will benefit mostly from a liver transplant and refer their patients before they develop more severe complications.”

As for future research, Venditti and colleagues will design future gene-based clinical trials using this new information while continuing to look for other ways in which FGF21 affects symptoms of MMA. – by Phil Neuffer

For more information:

Charles P. Venditti, MD, PhD , can be reached at the National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, 9000 Rockville Pike, Bethesda, MD 20892-2152; email:

Disclosure: Venditti reports that he has received research funding from Selecta Biosciences and LogicBio Therapeutics.