Navigation Links
High-fat diet and lack of enzyme can lead to heart disease in mice
Date:9/12/2011

PHILADELPHIA - It's no secret that a high-fat diet isn't healthy. Now researchers have discovered a molecular clue as to precisely why that is.

Writing in the Journal of Biological Chemistry, Mitchell Lazar, MD, PhD, the Sylvan Eisman Professor of Medicine and director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine at the University of Pennsylvania, and colleagues, describe that mice lacking a gene-expression-controlling enzyme fed a high-fat diet experience rapid thickening of the heart muscle and heart failure. This molecular link between fat intake and an enzyme tasked with regulating gene expression at least in mice has implications for people on so-called Western diets and combating heart disease. Modulating the enzyme's activity could be a new pharmaceutical target.

The team found that the engineered mice without the enzyme HDAC3 tended to underexpress genes important in fat metabolism and energy production. Essentially, when fed a high-fat diet, these animals' hearts cannot generate enough energy and thus cannot pump blood efficiently.

These same mice tolerate a normal diet as well as non-mutant, normal animals. "HDAC3 is an intermediary that normally protects mice from the ravages of a high-fat diet," says Lazar.

HDAC enzymes control gene expression by regulating the accessibility of chromatin - the DNA and protein structure in which genes reside. Within chromatin, DNA is wound around proteins called histones. Genes in tightly wound chromatin areas are generally inaccessible and suppressed, whereas those in loosely packed areas can be activated.

When an animal eats, its metabolism changes, but food doesn't change a cell's genome. Instead, food modulates the "epigenome," molecular markers on the chromatin that influence gene expression by affecting how tightly DNA is wrapped around its protein scaffolding.

Previously, researchers at the University of Texas Southwestern Medical Center showed that if HDAC3 were deleted in heart tissue in the middle of embryonic development, the animals developed severe thickening of the heart walls (hypertrophic cardiomyopathy) that reduces the organ's pumping efficiency. These animals usually died within months of birth.

Lazar and his team wanted to know what would happen if the gene was inactivated in heart tissue after birth. To their surprise, they found that these animals were essentially normal.

On a diet of regular chow, the engineered mice lived as long as their normal littermates, although they did tend to accumulate fat in their heart tissue. On a high-fat diet, however, these animals deteriorated rapidly, dying within a few months of hypertrophic cardiomyopathy and heart failure.

To understand why, Lazar's team compared the gene expression patterns of young mutant mice to their normal siblings. They found that the mutant mice tended to underexpress genes important in fat metabolism and energy production. Essentially, on a high-fat diet, these animals' hearts cannot generate enough energy and thus cannot pump blood efficiently.

According to Lazar, this study identifies an "interesting and dramatic example" of the link between diet and epigenetics. Now his team is working to identify the molecular nature of that link. They are also investigating whether the same pathway and interaction occurs in humans since it may contribute to the increased heart disease associated with Western diets.

Whatever the outcome of those studies, says Lazar, there is one sure-fire intervention people can always use to stave off the ravages of over-nutrition: Changing your diet. "We don't want to forget that that's still a noble thing to strive for," he says.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Gastric Bypass May Dampen Desire for High-Fat Foods
2. Eating a high-fat diet may rapidly injure brain cells that control body weight
3. Low-Carb, High-Fat Diets May Not Pose Risk to Arteries
4. High-fat diet during pregnancy programs child for future diabetes
5. Study reinforces link between obesity, high-fat meals and heart disease
6. Greater obesity in offspring of nursing mothers consuming a high-fat diet
7. A high-fat diet alters crucial aspects of brain dopamine signaling
8. High-fat ketogenic diet effectively treats persistent childhood seizures
9. High-Fat Meal May Trigger Asthma
10. High-fat ketogenic diet to control seizures is safe over long term
11. Inhibiting key enzymes kills difficult tumor cells in mice
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
High-fat diet and lack of enzyme can lead to heart disease in mice
(Date:2/13/2016)... ... February 13, 2016 , ... Christie Medical ... in-kind gift of a VeinViewer® Vision vein finder for the nursing ... start an IV and draw blood, combining technology with traditional technique. , “VeinViewer ...
(Date:2/12/2016)... ... 12, 2016 , ... According to an article published February 4th ... significant portion of hernia repairs throughout the United States. Commenting on this article, Beverly ... that this trend has not only been expected, but it seems to be a ...
(Date:2/12/2016)... ... February 12, 2016 , ... The Lymphoma ... innovative lymphoma research and serving the lymphoma community through a comprehensive series of ... South Florida’s philanthropic community at its 10th anniversary Fashion Luncheon on Monday, February ...
(Date:2/12/2016)... ... February 12, 2016 , ... As a former television executive, owner Tal Rabinowitz ... no time to decompress, Rabinowitz found herself drawn to a casual meditation class while ... on her life, implementing a 20-minute-per-day meditation practice with her team. After her tenure ...
(Date:2/12/2016)... , ... February 12, 2016 , ... ... Service (WaaS), today announced the integration of Clarity Intelligence Platform (CIP) into Cielo®, ... to offer real-time business intelligence (BI) to their small and medium business (SMB) ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... 12, 2016  Aralez Pharmaceuticals Inc. (Nasdaq: ARLZ ... Company will ring the Nasdaq Closing Bell at the ... at 4:00 p.m. ET on Tuesday, February ... Adrian Adams , will perform the honorary ... 4:00 p.m. ET.  A live webcast will be available ...
(Date:2/12/2016)... , 12 februari 2016 AAIPharma ... toonaangevende leverancier van productie en ontwikkeling op ... kondigt vandaag een uitbreiding aan van steriele ... locatie in Charleston, SC ... tot meerdere recente investeringen. http://photos.prnewswire.com/prnh/20150806/256637LOGO ...
(Date:2/12/2016)... , Ungarn, February 12, 2016 ... das sich auf den ungedeckten medizinischen Bedarf ... positive Ergebnisse seines klinischen Forschungsprogramms bekannt. Das ... beschäftigt, ergab Verbesserungen ihrer respiratorischen Funktionen und ... ltd , ein Medizintechnikunternehmen, das sich auf ...
Breaking Medicine Technology: