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Obesity is one of the major health problems of the western world, with the numbers of affected people rising dramatically in recent years. In the UK, levels have tripled since 1980 with one in four adults currently estimated to be within the official obesity bracket and over 50% of women and 66% of men declared overweight or obese. If the trend increases at the same rate, about 90% of adults will be overweight or obese by the year 2050. The incidence of obesity is similar in the USA, with all but one states having obesity rates of 25% or higher in 2007. The figures depend on the definition of obesity, which is related to the body mass index (BMI), calculated as the body weight (in kg) divided by the square of the height (in m). A BMI of more than 25 is regarded as overweight and a value greater than 30 is obese. Whether or not you agree with these limits, it is hard to argue against visual evidence. Just take a look around your local town. Obesity is drawing attention because it introduces an increased risk of illness, including type 2 diabetes and several types of cancer. Another association is with cardiovascular disease (CVD), for which cholesterol bound to low-density lipoprotein (LDL) has been implicated. High levels of LDL cholesterol are thought to deposit cholesterol within the arteries where it tends to remain, especially when there are low levels of high-density lipoprotein (HDL), a major factor for removing it. However, the identity of other proteins in LDL is often overlooked and they may also have an important role to play in the increased risk of CVD. In 2005, scientists in Sweden mapped the proteins in LDL and HDL in healthy people. Now, the same group has extended the work to determine, for the first time, the protein composition of LDL in obese adults (BMI > 30) compared with healthy controls (BMI < 25). Mats Lindahl, Helen Karlsson, Harriet Mortstedt and Christer Tagesson from Linkoping University and Helen Lindqvist from the Chalmers University of Technology, Goteborg, collected plasma from 19 apparently healthy, non-smoking subjects - 9 controls and 10 obese. The LDL fraction in the plasma was collected by density gradient ultracentrifugation and the proteins present were separated by 2D gel electrophoresis. After staining the protein spots with SYPRO Ruby dye, the various proteins were quantified relatively by measuring their fluorescence intensities as a percentage of the total protein fluorescence. Their identities were determined by MALDI TOF MS following digestion of each individual protein with trypsin and database searching. The team found that LDL from obese subjects contained reduced levels of apolipoprotein IV and the major isoform of apolipoprotein I. Conversely, it contained increased levels of apolipoprotein J, C-II and C-III, alpha-1-antitrypsin and the newly detected protein transthyretin. This has been found previously in HDL but has never been reported in LDL. The transthyretin levels in plasma were not markedly different between obese and control subjects, indicating that the increase in LDL really is an enrichment. Both transthyretin, a transport protein, and alpha-1-antitrypsin have been detected previously in human coronary atherosclerotic lesions and the research team declared that "it is tempting to speculate that these alterations in the LDL protein profile reflect a process that is linked to an increased risk of CVD," although further studies will be required to ascertain the clinical relevance. There were also some gender-related differences. Apolipoprotein E was reduced in obese men compared with controls but was unchanged in women. Apolipoprotein C-III was increased in obese men only. In addition, the most acidic form of apolipoprotein A-I was raised in women compared with men. This protein is thought to be susceptible to methionine oxidation, which has been implicated in CVD. The results indicate that obesity is accompanied by differences in the protein composition of LDL as well as that known for HDL. The methodology allows more detailed information to be gathered compared with cholesterol measurements or the typical biomarker experiments that measure a single protein or peptide in plasma. However, the researchers point out that the work should be regarded as a pilot study, due to the relatively small number of subjects. Much more testing is required to see if these observations can be generalised. Related links:
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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