Reducing liver protein SIRT1 levels

January 22, 2014

A new study led by Boston University School of Medicine (BUSM) demonstrates that the abnormal metabolism linked to obesity could be regulated in part by the interaction of two metabolic regulators, called the NAD-dependent deacetylase SIRT1 and fibroblast growth factor 21 (FGF21). Using experimental models, the researchers found that a lack of SIRT1 protein in the liver led to lower levels of a liver secreted protein FGF21, which resulted in an increased likelihood of developing fatty liver disease and obesity.

When levels of FGF21 in the liver of experimental models were elevated, some of the white became some of cells, producing more heat and burned calories. White fat stores energy as large fat droplets, while brown fat has much smaller fat droplets and is specialized to burn them, yielding heat. In humans, there is evidence that more brown fat is associated with a lower body weight. Finding a way to turn white fat into brown fat could potentially lead to a decrease in obesity and other metabolic diseases.

This study, which is published in Gastroenterology, was led by Mengwei Zang, MD, PhD, and her team in the department of medicine at BUSM.

In previous experiments, Zang's laboratory showed that elevated liver SIRT1 protein limited the development of fatty liver in when the diet was high in fat. However, the mechanism was not known. To determine how this happens, Zang laboratory used a unique mouse model that did not have liver SIRT1 protein, which resulted in an elevation in hepatic fat levels, an increase in body weight, and a decrease in nighttime oxygen consumption. It also led to decreased levels of liver FGF21, which were associated with abnormal fat metabolic changes in liver and adipose tissues.

However, when levels of liver and serum FGF21 were elevated, some white fat cells changed and became , which could increase whole-body oxygen consumption and produce more heat. These changes in the fat cells caused by elevated FGF21 protein could help explain how the experimental mice experienced more weight loss, had less and slowed the progression of fatty liver.

"Excess abdominal white fat in humans promotes heart disease, diabetes and other metabolic diseases, and it would be potentially therapeutic if we could transform white fat into brown fat by elevating FGF21 levels," said Zang, the study's corresponding author.

Explore further: Researchers determine hormone linked to improved glucose metabolism activates browning of fat

Related Stories

'Beige' cells key to healthy fat

January 17, 2014

"Beige fat" cells found in healthy subcutaneous fat in mice play a critical role in protecting the body from the disease risks of obesity, report researchers at Dana-Farber Cancer Institute, who say their study findings may ...

Recommended for you

Artificial beta cells

December 8, 2016

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers question lifelong immunity to toxoplasmosis

December 8, 2016

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.