Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Chattopadhyay, Arnab; Navab, Mohamad; Hough, Greg; Grijalva, Víctor; Mukherjee, Pallavi; Fogelman, Hannah R.; Hwang, Lih Hwa; Faull, Kym F.; Lusis, Aldons J.; Reddy, Srinivasa T.; Fogelman, Alan M.

doi:10.1194/jlr.m064352

Cited by 21 publications

(48 citation statements)

References 43 publications

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“…The decrease in oxidized phospholipids was associated with decreased inflammation in the jejunum and systemically42. We did not directly measure the level of the oxidized phospholipids formed in this study.…”

Section: Discussionmentioning

confidence: 85%

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ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Cedó

García-León

Baila-Rueda

et al. 2016

Sci Rep

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Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

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Section: Discussionmentioning

confidence: 85%

“…Recently, Chattopadhyay et al 42 reported that feeding mice a concentrate of transgenic tomatoes expressing the apoA-I mimetic peptide 6F decreased the formation of oxidized phospholipids in the jejunum. The decrease in oxidized phospholipids was associated with decreased inflammation in the jejunum and systemically42.…”

Section: Discussionmentioning

confidence: 99%

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Cedó

García-León

Baila-Rueda

et al. 2016

Sci Rep

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“…Functional cholesterol homeostasis relies on the conversion of cholesterol into bile acids and is required to prevent the accumulation of cholesterol, triglycerides and toxic metabolites in organs such as the liver (Chiang ). Recently, the effect of LPC 18:1 on atherogenesis was demonstrated in a study wherein increased levels of intestinal and systemic inflammation were observed in Ldlr ‐null mice fed dietary LPC 18:1 (Chattopadhyay et al ). Autotoxins promote atherosclerosis by converting LPC 18:1 and other unsaturated LPCs into inflammatory and atherogenic LPAs (Navab et al ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

et al. 2019

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Aims Epidemiological studies have correlated cardiovascular disease and atherosclerosis with lifestyle factors such as sedentary behaviour and a high‐calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low‐density lipoprotein receptor‐null (Ldlr−/−) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and proinflammatory mediators in the intestine and serum. Methods and Results Mice were maintained on a high‐fat diet with or without oral quercetin administration for 12 weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde and increased interleukin 6 levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum‐level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and caecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level. Conclusions This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites. Significance and Impact of the Study Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

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“…It is known that HDL assembled in areas of inflammation loses its anti‐inflammatory properties . Chattopadhyay et al . also demonstrated adding to the Western diet an apoA‐I mimetic peptide resembling 4F, Tg6F, dramatically suppressed oxidized phospholipid production and the related intense inflammatory response in the villus.…”

Section: Discussionmentioning

confidence: 99%

“…A plethora of immune cells surrounds the lymphatics and capillary tuft in the lamina propria. Chattopadhyay et al 28 fed mice a Western diet, and found oxidized phospholipids were formed in the lamina propria and provoked an intense inflammatory response in this area of the villus. It is known that HDL assembled in areas of inflammation loses its anti-inflammatory properties.…”

Section: Discussionmentioning

confidence: 99%

Oral Apolipoprotein A‐I Mimetic D‐4F Lowers HDL‐Inflammatory Index in High‐Risk Patients: A First‐in‐Human Multiple‐Dose, Randomized Controlled Trial

Dunbar

Movva

Bloedon

et al. 2017

Clinical Translational Sci

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A single dose of the apolipoprotein (apo)A‐I mimetic peptide D‐4F rendered high‐density lipoprotein (HDL) less inflammatory, motivating the first multiple‐dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D‐4F. High‐risk coronary heart disease (CHD) subjects added double‐blinded placebo or D‐4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D‐4F was safe and well‐tolerated. Mean ± SD plasma D‐4F area under the curve (AUC, 0–8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± 60.9 ng/mL*h (500 mg) among men, higher among women. Whereas placebo dropped HDL inflammatory index (HII) 28% 8 h postdose (range, 1.25–0.86), 300–500 mg D‐4F effectively halved HII: 1.35–0.57 and 1.22–0.63, respectively (P < 0.03 vs. placebo). Oral D‐4F peptide dose predicted HII suppression, whereas plasma D‐4F exposure was dissociated, suggesting plasma penetration is unnecessary. In conclusion, oral D‐4F dosing rendered HDL less inflammatory, affirming oral D‐4F as a potential therapy to improve HDL function.

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Tg6F ameliorates the increase in oxidized phospholipids in the jejunum of mice fed unsaturated LysoPC or WD

Cited by 21 publications

References 43 publications

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

Oral Apolipoprotein A‐I Mimetic D‐4F Lowers HDL‐Inflammatory Index in High‐Risk Patients: A First‐in‐Human Multiple‐Dose, Randomized Controlled Trial

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