News From The Journal Of Lipid Research

Articles to be published in the November 2007 issue of the Journal of Lipid Research (Vol. 48, No. 11):



Preventing Alzheimer's disease early on



Dayan B. Goodenowe and colleagues have shown that people with Alzheimer's disease and related conditions exhibit decreased blood levels of an important brain chemical called ethanolamine plasmalogen, even at the very early stages of the disease. The scientists have also found that this decrease is more pronounced when the symptoms are more severe.



Alzheimer's disease and related conditions, grouped under the name dementia of the Alzheimer's type (DAT), mostly affect elderly people. These conditions are not easily diagnosed because they can arise from many different causes, some of which that are not well known. Although the relationship between blood levels of ethanolamine plasmalogens and the severity of DAT is not completely understood, the new discovery may improve the diagnosis of DAT and help patients make decisions about how to cope with the disease.



The scientists suggest that the observed decrease of ethanolamine plasmalogens may result in decreased release and subsequent decreased activity of acetylcholine, a critical brain chemical involved in memory formation and whose activity is known to be reduced in DAT patients. So correcting the ethanolamine plasmalogen deficit in DAT may slow or correct the acetylcholine deficit in DAT patients.



The researchers conclude that clinical trials involving restoration of ethanolamine plasmalogens should be undertaken to determine its efficacy in the treatment and/or prevention of DAT.



Article: "Peripheral Ehanolamine Plasmalogen Deficiency: A Logical Causative Factor in Alzheimer's Disease and Dementia," by Dayan B. Goodenowe, Lisa L. Cook, Jun Liu, Yingshen Lu, Dushmanthi A. Jayasinghe, Pearson W.K. Ahiahonu, Doug Heath, Yasuyo Yamazaki, John Flax, Kevin F. Krenitsky, D. L. Sparks, Alan Lerner, Robert P. Friedland, Takashi Kudo, Kouzin Kamino, Takashi Morihara, Masatoshi Takeda, and Paul L. Wood



Improving the assessment of coronary heart disease risk in Chinese



Scientists report that the concentration of a compound called apolipoprotein B in the blood is better at predicting whether Chinese have coronary heart disease -- in which fatty deposits clog arteries that supply blood and oxygen to the heart -- than other substances such as blood cholesterol levels. This finding could help improve the diagnostic and treatment of coronary heart disease in Chinese and maybe in other populations as well.
















To diagnose the early stages of coronary heart disease, physicians usually measure levels of substances present in the blood, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B, which act as "markers" of the disease. But these markers are not very accurate and whether some of them are better at predicting the onset of the disease is not clear yet.



Kuo-Liong Chien, Yuan-Teh Lee and colleagues compared the levels of the markers in over 3,500 participants who did not have the disease at the time of recruitment but some of whom (122 individuals) developed the disease 13 years later. The scientists then compared which of the three substances would have best predicted the onset of the disease and found that the risk of developing coronary heart disease was more than three times as high in participants with the highest values of both apolipoprotein B and the ratio of the total cholesterol over HDL-C than patients who did not have the disease.



The scientists conclude that apolipoprotein B is more strongly associated than LDL-C with the risk of developing coronary heart disease. They add that non-HDL cholesterol is an important predictive factor for CHD among Chinese, more so than LDL cholesterol and that the ratio of total cholesterol over HDL cholesterol can strongly predict coronary heart disease.



Based on these results, the researchers recommend that apolipoprotein B should be included in the comprehensive evaluation of risk for this disease in Asian populations.



Article: "Apoliporotein B and non-high-density lipoprotein cholesterol and risk of coronary heart disease in Chinese," by Kuo-Liong Chien, Hsiu-Ching Hsu, Ta-Chen Su, Ming-Fong Chen, Yuan-Teh Lee, and Frank B. Hu



Slowing down the development of heart disease



Scientists have shown that a protein called transthyretin (TTR) that is present in the blood may accelerate the development of atherosclerosis -- a potentially fatal heart disease in which the arteries are progressively narrowed and hardened over time, reducing blood flow to the heart.



TTR has been shown to cleave a blood compound called apolipoprotein A-I (ApoA-I), which can produce structures called fibrils that are shaped like strands and accumulate in blood vessels. These fibrils have been observed in people with a mutation of the gene that makes ApoA-I, but whether cleavage by TTR promotes the formation of such fibrils has not been assessed yet.



Monica Mendes Sousa and colleagues determined that when ApoA-I is cleaved by TTR, it tends to form fibrils faster than the uncleaved ApoA-I. This discovery may provide new ways to treat people with atherosclerosis by stopping TTR from cleaving ApoA-I and slowing down the formation of fibrils in blood vessels



Article: "ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity," by Marcia Almeida Liz, Claudio M. Gomes, Maria Joao Saraiva, and Monica Mendes Sousa



Potential health benefits of fish oil in baby formula



Scientists report that adding long-chain polyunsaturated fatty acids -- typically found in fish oil -- to baby formula may help infants better regulate their blood sugar and make more proteins in their muscle cells. These results may help make better decisions when dealing with pre-term birth, low-birth weight, and feeding of infants in intensive care.



Although infant formula is now considered nutritionally acceptable for infants under the age of one year, its composition is not a perfect match with breast milk, so the nutritional content of infant formula is regularly refined. Recent improvements include the addition of long-chain n-3 fatty acids, which can improve brain and visual development.



To better understand the role of these n-3 fatty acids in the early development of babies, M. Carole Thivierge and colleagues investigated how these fatty acids affect protein metabolism in neonatal pigs. The scientists weaned 28 piglets at two days of age and raised them for a month on either a control formula that didn't contain the fatty acid or a "test" formula that contained 3.5 percent of the fatty acid from fish oil.



The researchers noticed that in the piglets that were fed the control formula, fewer proteins were produced in their body over time and, at the same time, their insulin became less effective at lowering blood sugar levels. But piglets that drunk the test formula showed increased protein production and their insulin was as effective at using the proteins in the test formula for their growth as when they were born.



The scientists also noticed that most of the long-chain n-3 fatty acids were absorbed by muscle cell membranes and replaced another type of fatty acid known to promote inflammation. The long-chain n-3 fatty acids were also added to fats called triglycerides, but they did not replace at a similar extent the pro-inflammatory fatty acids there.



These results show that the long-chain n-3 fatty acids are preferably taken up by cell membranes and favor cellular activities that make new proteins which otherwise quickly decline after birth. This preferential incorporation of long-chain n-3 fatty acids in membranes and their impact on cellular activities could help understand better the role of these fatty acids in the development and future health of piglets -- and presumably infants too.



The scientists conclude that elevated amounts of long-chain n-3 fatty acids in muscle membranes have beneficial effects on the early development of piglets and may help babies in regulating muscle growth that affect early development and future metabolic health.



Article: "Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in neonate piglets by differentially altering muscle lipid composition," by Karen Bergeron, Pierre Julien, Teresa A. Davis, Alexandre Myre, and M. Carole Thivierge







The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.



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