Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph

Wang, Fei; Kohan, Alison B.; Dong, H. Henry; Yang, Qing; Xu, Min; Huesman, Sarah; Lou, Dan; Hui, David Y.; Tso, Patrick

doi:10.1002/phy2.247

Cited by 23 publications

(26 citation statements)

References 42 publications

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“…Hu-apoC-III Tg mice are homozygous for the transgene, which retains the human apoC-III promoter to drive expression in the same tissue distribution pattern as the endogenous mouse apoC-III. Transgenic mice express both murine and human apoC-III, but have no compensatory changes in endogenous mouse apoC-III expression (14). In our colony, hu-apoC-III Tg mice have been extensively backcrossed to C57BL/6J mice, therefore we used our own colony of transgenic and C57BL/6J (WT) mice throughout these studies.…”

Section: Animalsmentioning

confidence: 99%

“…C57BL/6J or human apoC-III transgenic (hu-apoC-III Tg) mice [generously provided by Dr. H. Dong, University of Pittsburgh, and originally generated by Dr. Jan Breslow (14,16)] aged 8-12 weeks were used for the isolation of primary intestinal crypts. Hu-apoC-III Tg mice overexpress human apoC-III (at approximately five times normal murine apoC-III levels) and have fasting plasma TAG levels of 500-700 mg/dl.…”

Section: Animalsmentioning

confidence: 99%

“…apoC-III also stimulates hepatic synthesis and secretion of VLDLs (12,13). We have reported that mice overexpressing apoC-III have a delayed rate of lipid absorption and secretion into lymph (14). Though significant progress has been made in understanding the mechanisms that govern these plasma and hepatic effects of apoC-III, much less is known about the function of apoC-III in the intestinal lipoprotein synthesis pathway and its potential effect on the metabolism of dietary lipid and subsequent impact on CVD risk.…”

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confidence: 99%

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Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Jattan

Rodia

et al. 2017

Journal of Lipid Research

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The intestine plays a crucial role in regulating wholebody lipid homeostasis through dietary fat absorption and secretion, and through its endocrine secretions of incretin hormones and immune mediators. The intestine synthesizes a specialized lipoprotein, the chylomicron, which contains both dietary triglyceride (TAG) and cholesterol, in addition to both structural and functional apolipoprotein cargo. apoB-48 provides structure to the nascent chylomicron, while apoA-IV, apoA-I, and apoC-III function in the periphery to modify plasma lipid metabolism and clearance, interact with inflammatory apparatus for efficient clearance of dietary lipopolysaccharide and oxidized lipids, and modulate insulin signaling and glucose metabolism (1-3). Therefore, the intestine and its secreted chylomicron are critical regulators of metabolic disease.Despite the importance of the intestine in raising plasma TAG levels in the postprandial state and in apolipoprotein secretion, mechanistic studies are difficult to carry out. This is due to a lack of suitable ex vivo cell culture models that are nontransformed yet stable enough in culture for extended studies and genetic manipulations. The intestine is difficult to model ex vivo because enterocytes are in constant turnover, and are only replenished by intestinal stem cells

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Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

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Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Jattan

Rodia

et al. 2017

Journal of Lipid Research

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“…Likewise, higher abundance of DBI and ACOX1 was observed in this study, suggesting the stimulation of lipids β-oxidation for nutrient absorption to meet the energy requirement in the small intestine of NSPE pigs [55, 56]. Apolipoprotein C-III (APOC3) is an important modulator that is secreted from the intestine on the chylomicron upon lipid absorption [57]. The up-regulation of APOC3 implies the enhanced absorption of dietary lipids in the NSPE group.…”

Section: Discussionmentioning

confidence: 73%

Proteome changes in the small intestinal mucosa of growing pigs with dietary supplementation of non-starch polysaccharide enzymes

Zhang

Gao

et al. 2016

Proteome Sci

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BackgroundNon-starch polysaccharide enzymes (NSPEs) have long been used in monogastric animal feed production to degrade non-starch polysaccharides (NSPs) to oligosaccharides in order to promote growth performance and gastrointestinal (GI) tract health. However, the precise molecular mechanism of NSPEs in the improvement of the mammalian small intestine remains unknown.MethodsIn this study, isobaric tags were applied to investigate alterations of the small intestinal mucosa proteome of growing pigs after 50 days of supplementation with 0.6% NSPEs (mixture of xylanase, β-glucanase and cellulose) in the diet. Bioinformatics analysis including gene ontology annotation was performed to determine the differentially expressed proteins. A protein fold-change of ≥ 1.2 and a P-value of < 0.05 were selected as thresholds.ResultsDietary supplementation of NSPEs improved the growth performance of growing pigs. Most importantly, a total of 90 proteins were found to be differentially abundant in the small intestinal mucosa between a control group and the NSPE group. Up-regulated proteins were related to nutrient metabolism (energy, lipids, protein and mineral), immunity, redox homeostasis, detoxification and the cell cytoskeleton. Down-regulated proteins were primarily related to transcriptional and translational regulation. Our results indicate that the effect of NSPEs on the increase of nutrient availability in the intestinal lumen facilitates the efficiency of nutrient absorption and utilization, and the supplementation of NSPEs in growing pigs also modulates redox homeostasis and enhances immune response during simulating energy metabolism due to a higher uptake of nutrients in the small intestine.ConclusionsThese findings have important implications for understanding the mechanisms of NSPEs on the small intestine of pigs, which provides new information for the better utilization of this feed additive in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12953-016-0109-6) contains supplementary material, which is available to authorized users.

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“…causing accumulation of TG in the intestinal lumen ， setting a basis for its gastrointestinal regulation pathway (34).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Apoprotein C-III: A review of its clinical implications

Jin

Guo

2016

Clinica Chimica Acta

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Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph

Cited by 23 publications

References 42 publications

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

Proteome changes in the small intestinal mucosa of growing pigs with dietary supplementation of non-starch polysaccharide enzymes

Apoprotein C-III: A review of its clinical implications

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