Navigation Links
Abnormal fat metabolism underlies heart problems in diabetic patients
Date:8/13/2007

St. Louis, Aug. 10, 2007 Heart disease hits people with diabetes twice as often as people without diabetes. In those with diabetes, cardiovascular complications occur at an earlier age and often result in premature death, making heart disease the major killer of diabetic people. But why is heart disease so prevalent among diabetics?

To help answer that question, researchers at Washington University School of Medicine in St. Louis have been analyzing the fat (lipid) composition of heart tissue from laboratory mice with diabetes. They have found that heart cells of diabetic mice lose an important lipid from cellular components that generate energy for the heart, and their latest research shows this happens at the very earliest stages of diabetes.

"Diabetic hearts run mostly on fats for fuel because glucose isn't readily available to them," says Richard Gross, M.D., Ph.D., director of the Division of Bioorganic Chemistry and Molecular Pharmacology and professor of medicine, of chemistry and of molecular biology and pharmacology. "Unfortunately, this change in metabolism distorts the lipid composition of cell membranes causing abnormal physical properties and cellular dysfunction."

The important lipid that the researchers found to be decreased in diabetes is cardiolipin. "Cardiolipin" literally means heart fat, and the term was coined because cardiolipin was first discovered in beef hearts and is one of the most abundant lipids in heart tissue. This lipid has unusual physical properties that are essential for the operation of the energy-producing cell structures called mitochondria.

When mitochondria lose a lot of their cardiolipin, they malfunction. Their malfunction not only interferes with the energy supply of heart muscle cells, it also increases the amount of damaging oxygen-containing substances in the cells, creating unhealthy conditions that can lead to heart problems.

Interestingly, a rare genetic disorder Barth syndrome held a key to identifying cardiolipin decrease in diabetic hearts. Children born with Barth syndrome have weak hearts and often die young from heart failure. These children have mutations that prevent cells from producing enough cardiolipin. The connection between cardiolipin and heart disease in Barth syndrome led the Washington University researchers to wonder if cardiolipin was also affected in diabetic hearts.

But in order to measure cardiolipin, the researchers needed a way to distinguish it from the numerous other lipids found in heart cells. Fortunately, Gross and his colleagues have been developing and refining a highly sophisticated set of techniques that allow them to separate and quantify thousands of different lipids based on their subtle structural differences. The set of techniques has been termed "shotgun lipidomics" because they very rapidly determine which lipids are in tissues and blood.

"Shotgun lipidomics provide a precise way to measure changes in heart lipid content," says first author Xianlin Han, Ph.D., assistant professor of medicine. "We found a dramatic depletion of cardiolipin in heart muscle as early as five days after diabetes was induced in mice."

"These results suggest that cardiolipin alterations underlie heart dysfunction in diabetic heart disease and may be a useful biomarker for diagnosing cardiovascular disease in diabetes," Gross says. "Measuring alterations may be a way to tell the severity of heart disease and to evaluate how well therapies work. In addition, these findings suggest potential new therapeutic approaches."

Even though the research team found a depletion of an important type of lipid in diabetic heart tissue, diabetic heart muscle cells actually take in excess lipids. But as these lipids enter cells they activate lipid-digesting enzymes. In previous studies, Gross and colleagues identified a particular lipid-digesting enzyme that becomes more active in diabetic heart muscle and contributes to the breakdown of cardiolipin.

Recently, Gross and his colleague David Mancuso, Ph.D., member of the division, found that mice engineered to produce too much of this enzyme in their hearts developed defects in mitochondrial function which became worse when they were fasted a condition that, like diabetes, causes the heart to use lipids for fuel. A 16-hour fast caused significant problems with the mouse hearts' ability to pump blood, again implicating altered lipid metabolism, cardiolipin scarcity and mitochondrial impairment in heart disease using lipid as predominant fuel.

Gross adds that in addition to the effects on mitochondria, many of the membranes in heart cells, which are built from fatty molecules, are also adversely affected by the diabetic heart's abnormal lipid metabolism. Furthermore, because fatty molecules are part of cells' signaling mechanisms, numerous aspects of cellular physiology become altered.

"The pieces of the puzzle of diabetic heart disease are now rapidly falling into place," Gross says. "By exploiting the novel technology of shotgun lipidomics, we have identified the increased activation of certain lipid-digesting enzymes and the decrease of cardiolipin as central aspects of this disorder. We hope that these kinds of studies will enable physicians to diagnose diabetic cardiovascular disease sooner and treat it earlier."
'/>"/>
Contact: Gwen Ericson
314-286-0141
Washington University School of Medicine
Source:Eurekalert

Related biology news :

1. North & South American researchers find architectural abnormalities in T. cruzi ribosome
2. Model identifies genes that induce normal skin cells to become abnormal
3. Jefferson scientists identify gene defect leading to abnormal skin development and cancer
4. Whole-genome study at Johns Hopkins reveals a new gene associated with abnormal heart rhythm
5. Chromosomal abnormalities in sperm higher after vasectomy reversal
6. Abnormal overexpression of p53 is a predictive molecular biomarker
7. Opposing fat metabolism pathways triggered by a single gene
8. Attacks of King George IIIs madness linked to key metabolism molecule
9. Computational model simulates AZT metabolism in mitochondria
10. Researchers attack tumor cells by exploiting dependency on sugar metabolism
11. Huddling and a drop in metabolism allow penguins to survive the South Pole cold
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/15/2016)... Rico , Jan. 15, 2016 Recent ... and small to find new ways to ensure data ... iOS and Android that ... on biometrics, transforming it into a hardware authorization token. ... users swipe their fingerprint on their KodeKey enabled device ...
(Date:1/11/2016)... Calif. , Jan. 11, 2016 Synaptics ... human interface solutions, today announced that its ClearPad ® ... integration (TDDI) products won two separate categories in the ... Mobile Innovator and Best Technology Breakthrough. The Synaptics ® ... cost, a simplified supply chain, thinner devices, brighter displays ...
(Date:1/8/2016)... 8, 2016 NXTD ), a ... ® , a privately held leading direct seller of ... 5000 fastest-growing company announced that on December 31, ... million in Nxt-ID to develop a proprietary new wireless ... ® , a unique smart wallet that serves to ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... ... February 09, 2016 , ... ... innovations on its free and validated Electronic Data Capture (EDC) system ClinCaptureand its ... in Clinical Trials West Coast 2016 Conference in San Mateo, California on February ...
(Date:2/9/2016)... HOUSTON , Feb. 9, 2016 /PRNewswire/ ... virus-driven immunotherapies for cancer, announced that its ... the European Commission as an orphan medicinal ... the deadliest form of glioma, strikes approximately ... and EU. http://photos.prnewswire.com/prnh/20160208/330986LOGO ...
(Date:2/9/2016)... 9, 2016 DelveInsight,s, ... report provides in depth insights on the ... the Protein-Tyrosine Phosphatase 1B (PTP1B) Inhibitors. The ... various stages of development including Discovery, Pre-clinical, ... and Preregistration. Report covers the product clinical ...
(Date:2/8/2016)... Inc. today announced that Director Robert A. Ingram has ... addition, Robert Keegan has been appointed to the Board ... --> North Carolina . --> ... $32.8 million of net proceeds in a private Mezzanine B financing ... Research Triangle area of North Carolina . ...
Breaking Biology Technology: