Researchers at Washington University School of Medicine in St. Louis have linked abnormal fat metabolism to increased risk of heart disease in diabetics.
Earlier, Richard Gross and colleagues had found that an important lipid, cardiolipin, which has unusual physical properties that are essential for the operation of the energy-producing cell structures called mitochondria is decreased during diabetes.
AdvertisementWhen mitochondria lose a lot of their cardiolipin, they malfunction that not only interferes with the energy supply of heart muscle cells, but also increases the amount of damaging oxygen-containing substances in the cells, creating unhealthy conditions that can lead to heart problems.
Researchers identified a particular lipid-digesting enzyme that becomes more active in diabetic heart muscle and contributed to the breakdown of cardiolipin.
As part of this study, researchers used a highly sophisticated set of techniques called 'shotgun lipidomics' which very rapidly determine which lipids are in tissues and blood, to measure cardiolipin in engineered mice.
The study found that cardiolipin dramatic depleted in heart muscle as early as five days after diabetes was induced in mice.
Researchers found that mice engineered to produce too much of cardiolipin, developed defects in mitochondrial function, which worsened when they were, fasted, a condition that, like diabetes, causes the heart to use lipids for fuel.
The study found that 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.
Researchers also noted that in addition to the effects on mitochondria, many of the membranes in heart cells, which are built from fatty molecules, were also adversely affected by the diabetic heart's abnormal lipid metabolism. Furthermore, because fatty molecules are part of cells' signalling mechanisms, numerous aspects of cellular physiology become altered.
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