scholarly journals Lactobacillus acidophilus ATCC 4356 Prevents Atherosclerosis via Inhibition of Intestinal Cholesterol Absorption in Apolipoprotein E-Knockout Mice

2014 ◽  
Vol 80 (24) ◽  
pp. 7496-7504 ◽  
Author(s):  
Ying Huang ◽  
Jinfeng Wang ◽  
Guihua Quan ◽  
Xiaojun Wang ◽  
Longfei Yang ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Lactobacillus Acidophilus ◽  
Plasma Cholesterol ◽  
Cholesterol Absorption ◽  
Peroxisome Proliferator ◽  
Intestinal Cholesterol Absorption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Content Type ◽  
Apolipoprotein E Knockout Mice ◽  
Niemann Pick

ABSTRACTThe objective of this study was to investigate the effect ofLactobacillus acidophilusATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE−/−) mice. Eight-week-old ApoE−/−mice were fed a Western diet with or withoutL. acidophilusATCC 4356 daily for 16 weeks.L. acidophilusATCC 4356 protected ApoE−/−mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P< 0.05) higher in theL. acidophilusATCC 4356 treatment groups than in the control groups. Furthermore,L. acidophilusATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration ofL. acidophilusATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore,L. acidophilusATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.

scholarly journals The peroxisome-proliferator-activated receptor alpha agonist ciprofibrate severely aggravates hypercholesterolaemia and accelerates the development of atherosclerosis in mice lacking apolipoprotein E

2003 ◽  
Vol 373 (3) ◽  
pp. 941-947 ◽  
Author(s):  
Tao FU ◽  
Papreddy KASHIREDDY ◽  
Jayme BORENSZTAJN
Keyword(s):  
Apolipoprotein E ◽  
Plasma Cholesterol ◽  
Acid Oxidation ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Very Low Density Lipoproteins ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atherosclerotic Lesions ◽  
Deficient Mice

Mice lacking apolipoprotein E (apoE) are characterized by severe hypercholesterolaemia, caused by an abnormal accumulation of apolipoprotein B-48 (apoB-48)-carrying remnants of chylomicrons and very-low-density lipoproteins (VLDL) in the plasma, and by the spontaneous development of atherosclerotic lesions. Ciprofibrate is a hypolipidaemic compound that acts primarily by enhancing the oxidation of fatty acids in the liver and, consequently, decreasing the production of hepatic VLDL. In the present study, homozygous apoE-deficient mice were fed with a normal chow diet, supplemented with ciprofibrate. We report that, as anticipated, ciprofibrate treatment (a) stimulated hepatic fatty acid oxidation, as indicated by an increase in the mRNA levels of peroxisomal fatty acyl-CoA oxidase (AOX) and peroxisomal bifunctional enzyme, and (b) decreased the hepatic secretion of VLDL into the plasma, as determined by treating the animals with Triton WR-1339. Paradoxically, the apoE-deficient mice developed a 3–4-fold increase in their plasma cholesterol levels. A similar effect was observed in apoE-deficient mice treated with other peroxisome-proliferator-activated receptor α agonists (fenofibrate, bezafibrate and WY14,643). By FPLC of the plasma and Western-blot analysis, we determined that the enhanced hypercholesterolaemia was due to an increased accumulation of apoB-48-carrying lipoprotein remnants in the plasma. Consistent with this finding, atherosclerotic lesions in animals treated with ciprofibrate for 90 days were considerably more advanced than in untreated animals. These results indicate that the ciprofibrate-induced accumulation of apoB-48-carrying remnants in apoE-deficient mice is caused by the inhibition of an as yet uncharacterized apoE-independent mechanism of removal of remnant from the circulation by the liver.

scholarly journals Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle

2015 ◽  
Vol 308 (9) ◽  
pp. C710-C719 ◽  
Author(s):  
Anna Vainshtein ◽  
Liam D. Tryon ◽  
Marion Pauly ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Transmembrane Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Trafficking ◽  
Mitochondrial Transcription Factor ◽  
Energy Demands ◽  
Niemann Pick ◽  
Exercise Induced

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

scholarly journals A role for NPC1 and NPC2 in intestinal cholesterol absorption – the hypothesis gutted

2007 ◽  
Vol 408 (1) ◽  
Author(s):  
Laura Liscum
Keyword(s):  
Endoplasmic Reticulum ◽  
Dietary Cholesterol ◽  
Cholesterol Absorption ◽  
Cholesterol Transport ◽  
Intestinal Epithelial ◽  
Intestinal Cholesterol Absorption ◽  
Biochemical Journal ◽  
Good Target ◽  
Type C ◽  
Niemann Pick

Dietary and biliary cholesterol are taken up by intestinal epithelial cells and transported to the endoplasmic reticulum. At the endoplasmic reticulum, cholesterol is esterified, packaged into chylomicrons and secreted into the lymph for delivery to the bloodstream. NPC1L1 (Niemann–Pick C1-like 1) is a protein on the enterocyte brush-border membrane that facilitates cholesterol absorption. Cholesterol's itinerary as it moves to the endoplasmic reticulum is unknown, as is the identity of any cellular proteins that facilitate the movement. Two proteins that play an important role in intracellular cholesterol transport and could potentially influence NPC1L1-mediated cholesterol uptake are NPC1 and NPC2 (Niemann–Pick type C disease proteins 1 and 2). In this issue of the Biochemical Journal, Dixit and colleagues show that the absence or presence of NPC1 and NPC2 has no effect on intestinal cholesterol absorption in the mouse. Thus neither protein fills the gap in our knowledge of intra-enterocyte cholesterol transport. Furthermore, the NPC1/NPC2 pathway would not be a good target for limiting the uptake of dietary cholesterol.

scholarly journals ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice

2020 ◽  
Vol 127 (11) ◽  
pp. 1347-1361 ◽  
Author(s):  
Xin Bi ◽  
Takashi Kuwano ◽  
Paul C. Lee ◽  
John S. Millar ◽  
Li Li ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Lipoprotein Metabolism ◽  
Peroxisome Proliferator ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver Transcriptome ◽  
Artery Disease

Rationale: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated–like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. Objective: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. Methods and Results: ILRUN encodes a protein that contains a ubiquitin-associated–like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun -deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated–like domain of ILRUN was found to be required for its interaction with PPARα. Conclusions: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human.

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