News | August 17, 2011

Gladstone Scientist IDs Risk Factor Gene for Heart Disease, Diabetes

August 17, 2011 — A scientist at the Gladstone Institutes has discovered how a gene known as SIRT3 contributes to a suite of health problems, offering new insight into how to combat these potentially fatal conditions.

In a paper published in Molecular Cell, Gladstone Senior Investigator Eric Verdin, M.D., describes how SIRT3, when switched off, accelerates the build-up of fats throughout the body. This can lead to obesity, high blood pressure and a decreased ability to process sugar — the combination of which is known as the “metabolic syndrome.” Metabolic syndrome significantly increases one’s risk for developing heart disease and diabetes.

“Estimates indicate that one-third of Americans have the metabolic syndrome, and more develop it each year,” said Warner Greene, M.D., Ph.D., who directs virology and immunology research at Gladstone, an independent biomedical-research organization. He is also a professor of medicine, microbiology and immunology at the University of California-San Francisco (UCSF), with which Gladstone is affiliated. “By showing how the absence of SIRT3 can exacerbate obesity, Dr. Verdin’s group offers important clues concerning new ways to alleviate the symptoms of this American epidemic.”

To better understand the origins of obesity and this associated syndrome, Verdin and his colleagues deactivated the SIRT3 gene in laboratory mice. They fed the mice a high-fat diet and then observed the animals’ response at a molecular level.

Normally, SIRT3 sets off a complex chain of events to transform fat into energy at the cellular level. But deleting the SIRT3 gene disrupted this chain, and fat deposits weren’t broken down as they should have been.

Verdin further found that prolonged intake of a high-fat diet, even in normal mice, can itself reduce the activity of the enzyme produced by SIRT3 — an enzyme his laboratory originally discovered. The reduction in enzyme activity, in turn, leads to further fat build-up in places such as the bloodstream and liver. Over time, this build-up can lead to obesity, high blood pressure and insulin resistance.

Verdin and his colleagues also analyzed the SIRT3 genes of 8,000 Finnish men. This analysis pinpointed a single SIRT3 gene mutation present in 30 percent of the men. When present, the mutation reduced SIRT3 activity and increased risk for developing the metabolic syndrome.

“Finding a SIRT3 gene mutation linked to metabolic syndrome is a big step towards developing treatments for this increasingly common collection of obesity-related illnesses,” said Verdin, who is also a UCSF professor of medicine. “In the future, we hope to examine whether increasing SIRT3 activity can help decrease the symptoms of metabolic syndrome. We are also working to identify new drugs that can enhance the SIRT3 enzyme. Such drugs could be used in the future to stem the tide of the metabolic syndrome and its many complications.”

Other scientists who participated in the research at Gladstone include Matthew D. Hirschey, Tadahiro Shimazu, Carrie A. Grueter, Amy M. Collins, Bjoern Schwer and Robert V. Farese, Jr. Funding came from a wide variety of organizations including the Sandler Foundation, the Elison Medical Foundation, and the National Institute of Diabetes and Digestive and Kidney Diseases.

For more information: www.gladstone.ucsf.edu

Related Content

Sedentary Lifestyle Cancels Out Heart Benefits of Normal Weight
News | Cardiac Diagnostics | January 09, 2019
January 9, 2019 — Researchers at the University of Florida have found that low levels of physical activity can put he
Livongo Launches Applied Health Signals Product Category
News | Cardiac Diagnostics | November 30, 2018
Healthcare technology company Livongo recently announced the launch of its Applied Health Signals product category,...
HHS Releases Second Edition of Physical Activity Guidelines for Americans. #AHA2018 #AHA18
News | Cardiac Diagnostics | November 14, 2018
The U.S. Department of Health and Human Services (HHS) released the second edition of the Physical Activity Guidelines...
ACC and AHA Release Updated Cholesterol Guidelines for 2018. #AHA18 #AHA2018
Feature | Cardiac Diagnostics | November 13, 2018
November 13, 2018 — New cholesterol guidelines from the American Heart Association (AHA) and the American College of
AMI READMITS Score Predicts Heart Attack Patients at High Readmission Risk
News | Cardiac Diagnostics | October 09, 2018
Tracking just seven factors of heart attack patients when they are first admitted to the hospital can help flag those...
Siemens Healthineers Showcases New In Vivo and In Vitro Cardiovascular Solutions at TCT 2018
News | Cardiac Diagnostics | September 21, 2018
At the 2018 Transcatheter Cardiovascular Therapeutics (TCT) conference, Sept. 21-25 in San Diego, Siemens Healthineers...
Weight Loss Drug Does Not Increase Cardiovascular Events
News | Cardiac Diagnostics | August 31, 2018
A weight loss drug does not increase cardiovascular events, according to late breaking results from the CAMELLIA-TIMI...
Acarix Presents CADScor System at ESC 2018
News | Cardiac Diagnostics | August 27, 2018
Acarix AB’s ultra-sensitive acoustic CADScor System for coronary artery disease risk assessment will be on display at...
NIH Ending Funding for Moderate Alcohol and Cardiovascular Health Trial
News | Cardiac Diagnostics | August 24, 2018
The National Institutes of Health announced in June it plans to end funding to the Moderate Alcohol and Cardiovascular...
Study Shows Multiple Benefits of Patient-to-Patient Connectivity in Familial Chylomicronemia Syndrome
News | Cardiac Diagnostics | August 07, 2018
Akcea Therapeutics Inc., an affiliate of Ionis Pharmaceuticals Inc., announced the publication of results from the...
Overlay Init