scholarly journals Alcohol Pattern Consumption Differently Affects the Efficiency of Macrophage Reverse Cholesterol Transport in Vivo

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1885
Author(s):  
Daniela Greco ◽  
Simone Battista ◽  
Laura Mele ◽  
Antonio Piemontese ◽  
Bianca Papotti ◽  
...  

It has been well established that moderate alcohol consumption inversely correlates with cardiovascular morbidity and mortality, whereas binge alcohol drinking increases cardiovascular disease risk. The aim of this study was to assess in vivo the impact of different drinking patterns on reverse cholesterol transport (RCT); the atheroprotective process leading to the removal of excess cholesterol from the body. RCT was measured with a standardized, radioisotope-based technique in three groups of atherosclerosis-prone apolipoprotein E knock out mice: Placebo group, receiving water, which would mimic the abstainers; moderate group, receiving 0.8 g/kg alcohol/day for 28 days, which would mimic a moderate intake; binge group, receiving 0.8 g/kg alcohol/day for 5 days/week, followed by the administration of 2.8 g/kg alcohol/day for 2 days/week, which would mimic a heavy intake in a short period. Mice in the binge drinking group displayed an increase in total cholesterol, high density lipoprotein cholesterol (HDL-c) and non-HDL-c (all p < 0.0001 vs. placebo), and a significantly reduced elimination of fecal cholesterol. The moderate consumption did not lead to any changes in circulating lipids, but slightly improved cholesterol mobilization along the RCT pathway. Overall, our data confirm the importance of considering not only the total amount, but also the different consumption patterns to define the impact of alcohol on cardiovascular risk.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Lei Cai ◽  
Joseph D Layne ◽  
Sierra M Paxton ◽  
Courtney R Burkett ◽  
Richard Lee ◽  
...  

Excessive accumulation of cholesterol in the arteries drives atherosclerosis development. It is believed that biliary cholesterol secretion is crucial for eliminating excess cholesterol from the body via reverse cholesterol transport. In the current study, we wanted to determine the impact of reduced biliary cholesterol secretion on atherosclerosis development in mice. Decreased biliary cholesterol secretion was achieved by hepatic over-expression of human NPC1L1 (L1Tg mice) combined with knockdown of hepatic ABCG5/G8 function using an ABCG8 antisense oligonucleotide (ASO). LDLR-/- and LDLR-/-/L1Tg mice received either control or ABCG8 ASO and were fed a high fat (42% Kcal)/low cholesterol diet (0.015% wt/wt) for 20 weeks. As expected, L1Tg mice and mice with hepatic ABCG8 knockdown had an >70% reduction in biliary cholesterol. The dramatic decrease in biliary cholesterol did not increase plasma cholesterol, and in fact mice with hepatic ABCG8 knockdown had reduced VLDL cholesterol. Even more surprising, aortic atherosclerosis was significantly decreased in mice with compromised biliary cholesterol secretion. LDLR-/-/L1Tg treated with ABCG8 ASO had a >90% reduction in biliary cholesterol yet had ~70% less atherosclerosis compared to LDLR-/- controls. Moreover, reducing biliary cholesterol had no impact on macrophage reverse cholesterol transport, fecal excretion of neutral sterol, and hepatic expression of genes involved in cholesterol synthesis (HMG CoA reductase/synthase) and HDL metabolism (ABCA1 and SR-BI). These results indicate that atherosclerosis development can be decreased by shunting cholesterol away from biliary secretion and potentially towards trans-intestinal cholesterol excretion or bile acid synthesis.


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Ricquita D Pollard ◽  
Christopher N Blesso ◽  
Manal Zabalawi ◽  
Brian Fulp ◽  
Mark Gerelus ◽  
...  

Epidemiological studies have shown an inverse correlation between plasma high density lipoprotein (HDL) concentrations and cardiovascular disease risk. At variance with these observations, clinical trials that significantly raised plasma HDL-C levels did not have improved clinical outcomes, emphasizing the importance of understanding HDL function. Recently, a significant correlation has been reported between human procollagen c-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and HDL. PCPE2, a 52 kDa glycoprotein found in the extracellular matrix enhances cleavage of C-terminal procollagen by bone morphogenetic protein 1. Mice lacking PCPE2 have elevated concentrations of enlarged plasma HDL, a phenomenon associated with defective cholesterol efflux. HDL synthesis depends on ABCA1-mediated lipid efflux to lipid-poor apoA-I balanced by cholesterol uptake through hepatic scavenger receptor class B type I (SR-BI). Our studies focused on investigating if the elevated concentration of enlarged plasma HDL in PCPE2 deficient mice was atheroprotective. PCPE2 deficient mice were crossed with LDLr -/- mice (SKO) giving LDLr -/- , PCPE2 -/- (DKO) mice that had elevated HDL levels compared to SKO mice. Despite elevated HDL levels, we found that DKO mice had significantly more lipid and CD68+ infiltration into the aortic root, similar to that reported for LDLr -/- , apoA-I -/- mice that lack plasma apoA-I/HDL. Furthermore, DKO mice showed reduced HDL apoA-I fractional clearance and reverse cholesterol transport rates compared to SKO mice suggesting PCPE2 plays a significant role in HDL remodeling and/or cholesterol uptake by the liver. To test the effect of PCPE2 on SR-BI function we incubated 3 H-cholesteryl ether ( 3 H-CE) enriched HDL from SKO and DKO mice with CHO cells overexpressing PCPE2. Compared to CHO control cells, overexpression of PCPE2 increased 3 H-CE HDL uptake that was independent of HDL particle origin. Western Blot analysis showed no difference in SR-BI expression between control and PCPE2 transfected cells, suggesting that PCPE2 enhanced SR-BI function and promoted HDL cholesterol ester uptake. We conclude that PCPE2 is atheroprotective and an essential component of the reverse cholesterol transport system.


2002 ◽  
Vol 88 (3) ◽  
pp. 243-251 ◽  
Author(s):  
Enda J. Noone ◽  
Helen M. Roche ◽  
Anne P. Nugent ◽  
Michael J. Gibney

Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of linoleic acid. Studies using animal models have shown that CLA reduces adiposity, improves plasma lipoprotein metabolism and insulin sensitivity and reduces arteriosclerosis. Whilst CLA may have therapeutic potential with regard to coronary artery disease risk factors in human subjects, there has been little investigation into its effects in human subjects. This current study investigated the effects of dietary supplementation using two isomeric blends of CLA on triacylglycerol (TAG)-rich lipoprotein metabolism and reverse cholesterol transport in human subjects and evaluates whether CLA modulated cardiovascular disease risk factors. Fifty-one normolipidaemic subjects participated in this randomised double-blind placebo-controlled intervention trial. Subjects were randomly assigned to receive 3 g cis-9,trans-11–trans-10,cis-12 isomeric blend (50: 50) or a cis-9,trans-11–trans-10,cis-12 isomeric blend (80: 20) CLA or linoleic acid (control)/d for 8 weeks. The 50: 50 CLA isomer blend significantly reduced (P≤0·005) fasting plasma TAG concentrations. The 80: 20 CLA isomer blend significantly reduced (P≤0·05) VLDL-cholesterol concentrations. CLA supplementation had no significant effect on LDL-cholesterol, HDL-lipid-protein composition or reverse cholesterol transport. CLA supplementation had no effect on body weight, plasma glucose and insulin concentrations. Fatty acid analysis revealed that the cis-9,trans-11 CLA isomer was incorporated into total plasma lipids following supplementation with both isomeric blends of CLA. The present study demonstrates that CLA supplementation significantly improves plasma TAG and VLDL metabolism in human subjects. The study confirms that some of the cardio-protective effects of CLA that were shown in animal studies are relevant to man.


2021 ◽  
pp. 1-37
Author(s):  
Laury Sellem ◽  
Bernard Srour ◽  
Kim G. Jackson ◽  
Serge Hercberg ◽  
Pilar Galan ◽  
...  

Abstract In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for cardiovascular disease (CVD) prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥ 18 years from the NutriNet-Santé cohort (2009–2019). Daily dietary intakes were collected using 24h-dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n=1,952) included cerebrovascular (n=878 cases) and coronary heart diseases (CHD, n=1,219 cases). Multivariable Cox models were performed to investigate associations. This analysis included n=104,805 French adults (mean age at baseline 42.8 years (SD 14.6)), mean follow-up 5.5 years (SD 3.0, i.e. 579,155 persons years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared to intakes below 57 g/d (HR=0.81 [0.66-0.98], p-trend=0.01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomized controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2200 ◽  
Author(s):  
Unger ◽  
Torres-Gonzalez ◽  
Kraft

Lifestyle is a key modifiable risk factor involved in the manifestation of metabolic syndrome and, in particular, diet plays a pivotal role in its prevention and development. Current dietary guidelines discourage the consumption of saturated fat and dietary sources rich in saturated fat, such as dairy products, despite data suggesting that full-fat dairy consumption is protective against metabolic syndrome. This narrative review assessed the recent epidemiological and clinical research that examined the consumption of dairy-derived saturated fatty acids (SFA) on metabolic syndrome risk. In addition, this review evaluated studies of individual SFA to gain insight into the potential mechanisms at play with intake of a diet enriched with these dairy-derived fatty acids. This work underscores that SFA are a heterogenous class of fatty acids that can differ considerably in their biological activity within the body depending on their length and specific chemical structure. In summary, previous work on the impact of dairy-derived SFA consumption on disease risk suggests that there is currently insufficient evidence to support current dietary guidelines which consolidate all dietary SFA into a single group of nutrients whose consumption should be reduced, regardless of dietary source, food matrix, and composition.


2011 ◽  
Vol 7 (3) ◽  
pp. 1385-1394 ◽  
Author(s):  
Mozammel Haque ◽  
Jahirul Islam ◽  
Asiqur Rahaman ◽  
Fowzia Akter Selina ◽  
Mohammad Azizur Rahman ◽  
...  

Objective: Raphanus sativus is a hugely used edible root vegetable. We investigated whether the feeding of the Raphanus sativus hot water extract (RSE) ameliorates atherogenic lipid profile and oxidative stress in hypercholesterolemia. Methods: After feeding of the RSE to hypercholesterolemic rats for 6 weeks, the levels of plasma and hepatic total cholesterol (TC), triglyceride (TG), and plasma high density lipoprotein-cholesterol (HDL-C) and fecal TC levels were studied. The effects of RSE on the hepatic enzymes, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), the levels of lipid peroxide (LPO) and liver histology were also evaluated. Results: Hypercholesterolemia increased the levels of TC and TG in the plasma and livers. The levels of ALT, AST and ALP in plasma and LPO in the liver also increased. The dietary RSE, however, significantly ameliorated the above atherogenic lipids and liver enzymes. The RSE significantly reduced the levels of LPO in the liver, suggesting an in vivo protection against of oxidative stress. The RSE also inhibited the in vitro Fenton’s reagent-induced oxidative stress, thus corroborating the in vivo anti-LPO actions of RSE. The levels of hepatic LPO were positively correlated with plasma AST (r=0.76; P <0.05) and ALT (r=0.43; P<0.05) levels. Histologically, the livers of the RSE-fed hypercholesterolemic rats exhibited lesser fatty droplets and reduced inflammatory cells. Conclusion: Finally, R. sativus extract lowers the cardiovascular disease risk factors under hypercholesterolemic situation by increasing the plasma/hepatic clearance of cholesterol and improving the hypercholesterolemia-induced oxidative damage of hepatic tissues.


2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Xiuting Xu ◽  
Zikai Song ◽  
Bao Mao ◽  
Guoliang Xu

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.


10.2196/19053 ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. e19053
Author(s):  
Sean R Locke ◽  
Kaja Falkenhain ◽  
Dylan A Lowe ◽  
Terry Lee ◽  
Joel Singer ◽  
...  

Background Obesity and being overweight are major contributing factors for many diseases. Calorie restricted diets often fail to result in sustained long-term weight loss. Very low–carbohydrate, high-fat ketogenic diets have been suggested to have superior metabolic and weight loss effects. Keyto is a low-cost, highly scalable mobile health (mHealth) app paired with a noninvasive biofeedback tool aimed at facilitating weight loss through a personalized healthy and predominantly plant- and fish-based ketogenic diet. Objective This protocol describes a randomized trial comparing the efficacy of the Keyto mHealth app and device intervention to that of Weight Watchers’ WW app in individuals who are overweight or obese. The primary outcome is weight loss after 12 weeks. Secondary and exploratory outcomes, including metabolic and cardiovascular risk factors, will be assessed at 12, 24, and 48 weeks. Methods A total of 144 participants will be recruited and randomized to either the Keyto program or Weight Watchers program. Study participants will be guided through the study via video conference or phone calls and will undergo a fasting blood analysis performed by a third-party diagnostic lab at weeks 0 and 12 to assess metabolic and cardiovascular risk markers. All participants will be asked to weigh themselves daily on a study-provided Bluetooth-enabled scale. Participants randomized to the Keyto arm will also be asked to measure their breath acetone levels, a measure of ketosis, with the Keyto device 3 times per day. Results Recruitment started in December 2019. Rolling recruitment is expected to be completed by July 2020. Data collection and analysis of the primary intervention phase is expected to be completed in October 2020. The 24- and 48-week follow-ups are expected to be completed in January 2021 and July 2021, respectively. Conclusions This trial will provide high-quality evidence regarding the efficacy of the Keyto weight loss program in individuals who are overweight and obese in a free-living condition. This study also fills a gap by examining the impact of a ketogenic diet emphasizing plant- and fish-based fats on blood lipid profile and cardiovascular disease risk. Trial Registration ClinicalTrials.gov NCT04165707; https://clinicaltrials.gov/ct2/show/NCT04165707. International Registered Report Identifier (IRRID) DERR1-10.2196/19053


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