| Summary: | 碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 95 === Hypertriglyceridemia is a common, multifactorial metabolic disorder. The pathogenesis of this disease is not altogether clear, but it clearly involves in genetic variation of lipoprotein lipase（LPL）, a key enzyme in lipid metabolism. Pei et al preciously reported that two LPL variants with significant proportion（15-21％） were significantly associated with hypertriglyceridemia, called risk haplotypes. Therefore, the aim of this in-vitro experiment was to investigate that if these risk halotypes on LPL had any influence on the LPL protein expression and activity level. Four immortalized lymphocyte cell lines were used in the present study: two lines carried both risk haplotypes and two lines carried both protective haplotypes for hypertriglyceridemia. Basal level of LPL protein expression and activity were measured in both groups of cell lines. Then, lymphocytes in both groups were cultured for 24 h with 0.1, 0.2, 0.3 and 0.4 mmol/L unsaturated fatty acids（oleic acid[OA], arachidonic acid[AA], linoleic acid[LA] and eicosapentaenoic acid[EPA]）and lymphocyte LPL protein expression and activity were measured at the end of this incubation period. The results show that there was no significant difference in LPL protein expression between lymphocytes with protective and with risk haplotypes whether or not they were treated with fatty acids. However, the basal level of LPL activity were higher in lymphocytes with risk haplotypes than in those with protective haplotypes（P=0.0002）. Furthermore, incubation of lymphocytes with fatty acids decreased LPL activity in both groups and the inhibition of LPL activity are stronger in lymphocytes with risk haplotypes after OA and AA treatment. Overall, these results demonstrated that the basal level of LPL activity was higher and the inhibition of LPL activity is stronger in lymphocytes with risk haplotypes after fatty acids treatment than its counterpart. The difference in LPL activity suggested that the function of LPL is different in lymphocytes with risk and in those with protective haplotypes, but how does the functional difference cause hypertriglyceridemia needs further studies.
|
|---|
