The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 11 No.
4 • July 2008
Effects of Various Types of Fats on Heart Cells
The ability to measure changes in gene expression through the use of gene microarrays has led to deep insights into the effects of nutrients on physiological functions. In a very interesting recent study, researchers exposed adult rat cardiomyocytes (heart muscle cells) to individual fatty acids, including octanoate (the main fatty acid in medium-chain triglycerides), palmitate (long-chain saturated fat), stearate (long-chain saturated fat), oleate (oleic acid, monounsaturated fat), and linoleate (linoleic acid, polyunsaturated fat), and determined their effect on about 22,000 genes, looking for significant differences among the effects of the different fatty acids.
The most important findings were that the long-chain unsaturated fatty acids (oleate and linoleate) induced genes that promote fat oxidation (beta-oxidation, the use of fats as a metabolic fuel), whereas the long-chain saturated fatty acids (palmitate and stearate) induced genes associated with endoplasmic reticulum (ER) stress and oxidative stress. (The endoplasmic reticulum is a cellular structure that, among other things, is responsible for manufacturing and properly folding proteins. ER stress is a state in which there is a pileup of improperly folded proteins, requiring the ER to temporarily stop synthesizing proteins and to attempt to speed up the disposal of misfolded proteins.)
For example, carnitine palmitoyltransferase transfers fatty acids to mitochondria for beta-oxidation. One of the genes upregulated 4.3-fold by oleate was cpt1a (carnitine palmitoyltransferase 1A); the other fatty acids had no significant effect. Uncoupling protein 3 (ucp3) protects heart cells against apoptosis (a form of programmed cell death); a study by another researcher reported here showed that ucp3 is cardioprotective during ischemia/reperfusion. The microarray results showed that, acutely (6 hr), stearate, palmitate, and oleate induced ucp3 to a similar extent, but the response of ucp3 was transient for palmitate and stearate, whereas the effect of oleate persisted chronically (24 hr). Glutathione synthetase (activates synthesis of the major cellular antioxidant glutathione) was induced by palmitate 1.8-fold compared to no significant effects for the other fatty acids, suggesting a response to oxidative stress induced by palmitate.
- Lockridge et al. Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids. J Lipid Res 49:1395-1408 (2008).