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

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

January 9, 2014
Researchers at Joslin Diabetes Center have discovered that a hormone long associated with weight loss and improved glucose metabolism is linked to activation of calorie-burning brown fat. This finding could have implications ...

Newly discovered brown fat cells hold possibilities for treating diabetes, obesity

November 21, 2013
Obesity and diabetes have become a global epidemic leading to severe cardiovascular disease. Researchers at the University of Utah believe their recent identification of brown fat stem cells in adult humans may lead to new ...

Study discovers new regulators of the most prevalent liver disease

January 7, 2014
Excessive alcohol consumption, as well as obesity leads to the accumulation of fat in the liver, a disease termed fatty liver disease (FLD) or steatosis. FLD is one of the most prevalent diseases in Western societies and ...

'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 ...

Study unlocks origin of brown fat cells important in weight maintenance

September 26, 2013
In ongoing research aimed at battling obesity, UT Southwestern Medical Center researchers have deciphered how new fat cells are formed in energy-storing fat pads.

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

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.