Navigation Links
Scientists ID molecular 'switch' in liver that triggers harmful effects of saturated and trans fats

Dana-Farber Cancer Institute researchers have identified a molecular mechanism in the liver that explains, for the first time, how consuming foods rich in saturated fats and trans-fatty acids causes elevated blood levels of cholesterol and triglycerides and increases one's risk of heart disease and certain cancers.

In the Jan. 28 issue of Cell, scientists led by Bruce Spiegelman, PhD, report that the harmful effects of saturated and trans fats are set in motion by a biochemical switch, or co-activator, in liver cells called PGC-1beta.

Until now, scientists lacked a detailed explanation of how saturated and trans fats caused an increase in blood cholesterol and triglycerides, while diets high in unsaturated and polyunsaturated fats did not. Evidence pointed to the liver, which is responsible for the body's synthesis of triglycerides and cholesterol, but the molecular chain of events from eating fats to the buildup of cholesterol and triglycerides in the blood were unknown.

"What we have found is a missing link, a mechanism by which saturated fats and trans fats can do their dirty work," said Spiegelman, who carries out basic research on fat cells and metabolic pathways in diabetes and cancer at Dana-Farber. "It offers the opportunity to try to understand what makes these fatty acids so deleterious, and what we need to avoid."

Moreover, it is possible that in the future, drug therapy might be used to "turn down" the mechanism, decreasing cholesterol levels and heart disease risk, explained Spiegelman, who is also a professor of cell biology at Harvard Medical School.

Saturated fats are found in fatty cuts of meat, whole-milk dairy products, butter, and palm and coconut oils; they are associated with higher risk of coronary disease. The healthier polyunsaturated fats are those that remain liquid at room temperature, such as various types of vegetable oils.

Trans-unsaturated fatty acids, or trans fats, are artificially prod uced solid fats used in shortening and margarine, baked goods, and the oils used to cook french fries and other fast food. Studies have shown that trans fats not only raise LDL levels in the bloodstream but lower high-density lipoproteins (HDL, or "good" cholesterol) and may have even stronger adverse effects than do saturated fats.

The researchers report that when activated by harmful fats, PGC-1beta alters liver metabolism through a cascade of biochemical signals. The result is an upsurge in the liver's production of very low-density lipoprotein (VLDL) cholesterol, the precursor of low-density lipoprotein (LDL) cholesterol (known as the "bad" form of cholesterol) and triglycerides ?another fatty substance ?that are secreted into the bloodstream.

PGC-1beta belongs to a specific family of co-activators, proteins that interact with other proteins to turn genes on and off and adjust their activity, like a dimmer switch that varies the brightness of a light. Co-activators join with other regulatory proteins called transcription factors in controlling the expression of genes. Spiegelman and Jiandie Lin, PhD, the paper's lead author and a researcher at Dana-Farber, have previously discovered the PGC-1 co-activator family and several of its biochemical activities.

The Dana-Farber researchers made the discovery in searching for the function of PGC-1beta co-activator that was isolated in 2002. Experiments including the measurement of gene activity by microarrays showed that saturated and trans fats caused greater activity of the gene that makes PGC-1beta co-activator than did unsaturated fats.

The research also showed that when the fats triggered PGC-1beta, the co-activator interacted physically and turned up the function of sterol responsive element binding proteins. These important parts of the mechanism activate many key genes of lipid biosynthesis involving the pathways of cholesterol and triglycerides; these genes directed the liver to m anufacture more cholesterol, which it does in the form of very low-density lipoproteins. The investigators noted that in mice fed high-fat diets, the PCG-1beta mechanism actually decreased cholesterol in the liver while increasing it in the bloodstream.

"Before this report, it wasn't clear what the differences were between saturated fats and unsaturated fats in their ability to raise cholesterol blood levels," commented Jeffrey Flier, MD, an obesity specialist at Beth Israel Deaconess Medical Center. "These are important findings in a long-established area of medicine."


'"/>

Source:Dana-Farber Cancer Institute


Related biology news :

1. Scientists Replicate Hepatitis C Virus in Laboratory
2. Scientists detect probable genetic cause of some Parkinsons disease cases
3. Scientists find missing enzyme for tuberculosis iron scavenging pathway
4. Scientists seek answers on what activates deadly anthrax spores
5. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
6. Scientists collaborate to assess health of global environment
7. Scientists decipher genome of fungus that can cause life-threatening infections
8. Scientists discover the cellular roots of graying hair
9. Scientists rid stem cell culture of key animal cells
10. Scientists develop new color-coded test for protein folding
11. Scientists identify genetic pathways essential to RNA interference
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:12/20/2016)... , Dec. 20, 2016 The rising ... rental and leasing is stoking significant interest in ... frequency technology, Bluetooth low energy (BLE), biometrics and ... the next wave of wireless technologies in the ... system to advanced access systems opens the market ...
(Date:12/19/2016)... TORONTO , 19 de diciembre de 2016  Mosaic ... permitirá el desarrollo acelerado de MSC-1, un anticuerpo humanizado que se ... tumor en 2017, con múltiples sitios previstos a lo largo de ... ... el factor inhibidor de leucemia (LIF), una citoquina pleiotrópica que se ...
(Date:12/16/2016)... , Dec 16, 2016 Research and ... System Market - Global Forecast to 2021" report to their ... The ... to grow at a CAGR of 14.06% from 2016 to 2021. ... and is projected to reach 854.8 Million by 2021. The growth ...
Breaking Biology News(10 mins):
(Date:1/17/2017)... , Jan. 17, 2017  Protagonist Therapeutics, Inc. ... it has initiated a global Phase 2b induction ... peptide that targets alpha4beta7 integrin. The aim of ... to evaluate the safety/tolerability and efficacy of PTG-100 ... moderate to severe active disease. ...
(Date:1/16/2017)... , Jan. 16, 2017  Eurofins Genomics today announced ... allow more customers to receive their primers in a ... compromise in quality found with other providers. Express oligos ... States at no additional fee. ... genetic studies, including DNA sequencing, genotyping, site-directed mutagenesis, and ...
(Date:1/13/2017)... ... January 13, 2017 , ... Two Kalamazoo entrepreneurs have ... fulvic acid that farms, greenhouses and hydroponics operations use to increase yields and ... fastest growing segments of customers using this high grade fulvic acid extracted from ...
(Date:1/12/2017)... ... January 12, 2017 , ... ... of performing routine electrochemical biosensing has increased dramatically. Primarily driven by the ... and quantification of various analytes in complex samples. , Screen-printed ...
Breaking Biology Technology: