Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
This study investigates the developmental changes of the lipoprotein lipase （LPL） mRNA level in sheep muscle and its effect on intramuscular fat （IMF） accumulation. Male Kazak and Xinjiang Merino sheep at 2-120 da...This study investigates the developmental changes of the lipoprotein lipase （LPL） mRNA level in sheep muscle and its effect on intramuscular fat （IMF） accumulation. Male Kazak and Xinjiang Merino sheep at 2-120 days old were selected. Six animals of each breed were slaughtered at 2, 30, 60, 90, and 120 days （only the Xinjiang Merino sheep at 120-day old were available） to collect samples from longissimus dorsi muscle for the purpose of determining the IMF content and extracting total RNA that was used to investigate the developmental changes of the LPL mRNA expression by real-time PCR. The results showed that in male Kazak sheep, the IMF content increased with the progress of development and there were significant differences （P〈0.05） between the age groups. However, there was no difference （P〉0.05） between age groups in Xinjiang Merino sheep. Furthermore, the IMF content of the male Kazak sheep was significantly higher （P 〈 0.01） than that of the Xinjiang Merino sheep aged from 30 to 90 days. The highest LPL mRNA expression appeared at day 2 and it was significantly higher than that of all other age groups （P 〈 0.01）, while animals at 60-day old had the lowest LPL mRNA expression in the male Kazak sheep. In Xinjiang Merino sheep, the highest one occurred at 30-day old （P〈0.01）, followed by a continuous decrease to the lowest level at 90-day old, and then it started to increase slightly. At 2 to 60-day old, the LPL mRNA expression was negatively correlated to the IMF content （r=-0.625, P 〈 0.05） in male Kazak sheep, but no such relationship was detected in the male Xinjiang Merino sheep.展开更多
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
文摘This study investigates the developmental changes of the lipoprotein lipase （LPL） mRNA level in sheep muscle and its effect on intramuscular fat （IMF） accumulation. Male Kazak and Xinjiang Merino sheep at 2-120 days old were selected. Six animals of each breed were slaughtered at 2, 30, 60, 90, and 120 days （only the Xinjiang Merino sheep at 120-day old were available） to collect samples from longissimus dorsi muscle for the purpose of determining the IMF content and extracting total RNA that was used to investigate the developmental changes of the LPL mRNA expression by real-time PCR. The results showed that in male Kazak sheep, the IMF content increased with the progress of development and there were significant differences （P〈0.05） between the age groups. However, there was no difference （P〉0.05） between age groups in Xinjiang Merino sheep. Furthermore, the IMF content of the male Kazak sheep was significantly higher （P 〈 0.01） than that of the Xinjiang Merino sheep aged from 30 to 90 days. The highest LPL mRNA expression appeared at day 2 and it was significantly higher than that of all other age groups （P 〈 0.01）, while animals at 60-day old had the lowest LPL mRNA expression in the male Kazak sheep. In Xinjiang Merino sheep, the highest one occurred at 30-day old （P〈0.01）, followed by a continuous decrease to the lowest level at 90-day old, and then it started to increase slightly. At 2 to 60-day old, the LPL mRNA expression was negatively correlated to the IMF content （r=-0.625, P 〈 0.05） in male Kazak sheep, but no such relationship was detected in the male Xinjiang Merino sheep.
