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Special Issue "Lipoprotein Metabolism and Atherosclerosis"

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (28 February 2015)

Special Issue Editor

Guest Editor
Prof. Dr. Gloria Lena Vega

Center for Human Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9052, USA
Website | E-Mail
Phone: +1 214 648 2869
Fax: +1 214 648 4839
Interests: lipid and lipoprotein metabolism in atherosclerosis, diabetes mellitus, obesity

Special Issue Information

Dear Colleagues,

Atherosclerosis of the coronary arteries is a multifactorial disease that accounts for the majority of deaths in adult men and women in the industrialized world. Key physiologic risk factors for atherosclerosis include sex, age, plasma levels of Low Density Lipoprotein cholesterol (LDL C), and its precursors (VLDL and IDL), and HDL, and increased blood pressure. Susceptibility for risk is also imparted by obesity and by genetic pre-disposition to the disease. The major environmental risk factors include smoking, high intake of pro-atherogenic saturated fat in diet, and a sedentary lifestyle.

This supplemental issue of Nutrients focuses on advances in "Lipid and Lipoprotein Metabolism as a Risk for Atherosclerosis". The scope of topics of interest extends to diet and drugs with emphasis on mechanisms of action on their hypolipidemic effects.” Specific nutrients and/or drugs can be discussed based on the metabolic pathways targeted.

Prof. Dr. Gloria Lena Vega
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs).

Published Papers (9 papers)

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Research

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Open AccessArticle Low-Normal Thyroid Function and Novel Cardiometabolic Biomarkers
Nutrients 2015, 7(2), 1352-1377; doi:10.3390/nu7021352
Received: 7 December 2014 / Revised: 16 January 2015 / Accepted: 4 February 2015 / Published: 16 February 2015
Cited by 4 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
The concept is emerging that low-normal thyroid function, i.e., either higher thyroid-stimulating hormone or lower free thyroxine levels within the euthyroid reference range, could contribute to the development of atherosclerotic cardiovascular disease. It is possible that adverse effects of low-normal thyroid function
[...] Read more.
The concept is emerging that low-normal thyroid function, i.e., either higher thyroid-stimulating hormone or lower free thyroxine levels within the euthyroid reference range, could contribute to the development of atherosclerotic cardiovascular disease. It is possible that adverse effects of low-normal thyroid function on cardiovascular outcome may be particularly relevant for specific populations, such as younger people and subjects with high cardiovascular risk. Low-normal thyroid function probably relates to modest increases in plasma total cholesterol, low density lipoprotein cholesterol, triglycerides and insulin resistance, but effects on high density lipoprotein (HDL) cholesterol and non-alcoholic fatty liver disease are inconsistent. Low-normal thyroid function may enhance plasma cholesteryl ester transfer, and contribute to an impaired ability of HDL to inhibit oxidative modification of LDL, reflecting pro-atherogenic alterations in lipoprotein metabolism and HDL function, respectively. Low-normal thyroid function also confers lower levels of bilirubin, a strong natural anti-oxidant. Remarkably, all these effects of low-normal thyroid functional status appear to be more outspoken in the context of chronic hyperglycemia and/or insulin resistance. Collectively, these data support the concept that low-normal thyroid function may adversely affect several processes which conceivably contribute to the pathogenesis of atherosclerotic cardiovascular disease, beyond effects on conventional lipoprotein measures. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)

Review

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Open AccessReview Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance
Nutrients 2015, 7(11), 9127-9138; doi:10.3390/nu7115454
Received: 17 August 2015 / Revised: 7 October 2015 / Accepted: 9 October 2015 / Published: 5 November 2015
Cited by 11 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such
[...] Read more.
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Phytosterols, Phytostanols, and Lipoprotein Metabolism
Nutrients 2015, 7(9), 7965-7977; doi:10.3390/nu7095374
Received: 7 August 2015 / Revised: 8 September 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
Cited by 6 | PDF Full-text (118 KB) | HTML Full-text | XML Full-text
Abstract
The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and,
[...] Read more.
The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be diminished. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Hepatic Steatosis as a Marker of Metabolic Dysfunction
Nutrients 2015, 7(6), 4995-5019; doi:10.3390/nu7064995
Received: 8 April 2015 / Revised: 5 June 2015 / Accepted: 15 June 2015 / Published: 19 June 2015
Cited by 17 | PDF Full-text (1313 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds
[...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of the complex metabolic derangements associated with obesity. NAFLD is characterized by excessive deposition of fat in the liver (steatosis) and develops when hepatic fatty acid availability from plasma and de novo synthesis exceeds hepatic fatty acid disposal by oxidation and triglyceride export. Hepatic steatosis is therefore the biochemical result of an imbalance between complex pathways of lipid metabolism, and is associated with an array of adverse changes in glucose, fatty acid, and lipoprotein metabolism across all tissues of the body. Intrahepatic triglyceride (IHTG) content is therefore a very good marker (and in some cases may be the cause) of the presence and the degree of multiple-organ metabolic dysfunction. These metabolic abnormalities are likely responsible for many cardiometabolic risk factors associated with NAFLD, such as insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Understanding the factors involved in the pathogenesis and pathophysiology of NAFLD will lead to a better understanding of the mechanisms responsible for the metabolic complications of obesity, and hopefully to the discovery of novel effective treatments for their reversal. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis
Nutrients 2015, 7(6), 4453-4464; doi:10.3390/nu7064453
Received: 5 March 2015 / Revised: 13 May 2015 / Accepted: 27 May 2015 / Published: 3 June 2015
Cited by 6 | PDF Full-text (435 KB) | HTML Full-text | XML Full-text
Abstract
Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in
[...] Read more.
Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR) pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF)-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Effect of Dietary Fatty Acids on Human Lipoprotein Metabolism: A Comprehensive Update
Nutrients 2015, 7(6), 4416-4425; doi:10.3390/nu7064416
Received: 18 March 2015 / Revised: 26 May 2015 / Accepted: 29 May 2015 / Published: 2 June 2015
Cited by 4 | PDF Full-text (119 KB) | HTML Full-text | XML Full-text
Abstract
Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high
[...] Read more.
Dyslipidemia is a major risk factor for cardiovascular disease (CVD). Dietary fatty-acid composition regulates lipids and lipoprotein metabolism and may confer CVD benefit. This review updates understanding of the effect of dietary fatty-acids on human lipoprotein metabolism. In elderly participants with hyperlipidemia, high n-3 polyunsaturated fatty-acids (PUFA) consumption diminished hepatic triglyceride-rich lipoprotein (TRL) secretion and enhanced TRL to low-density lipoprotein (LDL) conversion. n-3 PUFA also decreased TRL-apoB-48 concentration by decreasing TRL-apoB-48 secretion. High n-6 PUFA intake decreased very low-density lipoprotein (VLDL) cholesterol and triglyceride concentrations by up-regulating VLDL lipolysis and uptake. In a study of healthy subjects, the intake of saturated fatty-acids with increased palmitic acid at the sn-2 position was associated with decreased postprandial lipemia. Low medium-chain triglyceride may not appreciably alter TRL metabolism. Replacing carbohydrate with monounsaturated fatty-acids increased TRL catabolism. Trans-fatty-acid decreased LDL and enhanced high-density lipoprotein catabolism. Interactions between APOE genotype and n-3 PUFA in regulating lipid responses were also described. The major advances in understanding the effect of dietary fatty-acids on lipoprotein metabolism has centered on n-3 PUFA. This knowledge emphasizes the importance of regulating lipoprotein metabolism as a mode to improve plasma lipids and potentially CVD risk. Additional studies are required to better characterize the cardiometabolic effects of other dietary fatty-acids. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Unique Features of High-Density Lipoproteins in the Japanese: In Population and in Genetic Factors
Nutrients 2015, 7(4), 2359-2381; doi:10.3390/nu7042359
Received: 23 December 2014 / Revised: 9 February 2015 / Accepted: 25 February 2015 / Published: 2 April 2015
Cited by 3 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density
[...] Read more.
Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL) levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Accordingly, lower HDL seems to contribute more to the development of coronary heart disease (CHD) than an increase in non-HDL lipoproteins at a population level in Japan. Interestingly, average HDL levels in Japan have increased further in the past two decades, and are markedly higher than in Western populations. The reasons and consequences for public health of this increase are still unknown. Simulation for the efficacy of raising HDL cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent by reducing low-density lipoprotein cholesterol predicted by simulation or achieved in a statin trial. On the other hand, a substantial portion of hyperalphalipoproteinemic population in Japan is accounted for by genetic deficiency of cholesteryl ester transfer protein (CETP), which is also commonly unique in East Asian populations. It is still controversial whether CETP mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential screening factor for historic accumulation of CETP deficiency in East Asia. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Open AccessReview Alcohol: A Nutrient with Multiple Salutary Effects
Nutrients 2015, 7(3), 1992-2000; doi:10.3390/nu7031992
Received: 10 February 2015 / Accepted: 11 March 2015 / Published: 18 March 2015
PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
Numerous studies have shown that cardiovascular disease is lower among alcohol consumers than among nonconsumers. Many of the metabolic effects of alcohol are mediated by its terminal metabolite, acetate, which has reported insulinemic properties. There have been few rational metabolic targets that underly
[...] Read more.
Numerous studies have shown that cardiovascular disease is lower among alcohol consumers than among nonconsumers. Many of the metabolic effects of alcohol are mediated by its terminal metabolite, acetate, which has reported insulinemic properties. There have been few rational metabolic targets that underly its cardioprotective effects until it was reported that acetate, the terminal product of alcohol metabolism, is the ligand for G-protein coupled receptor 43 (GPCR43), which is highly expressed in adipose tissue. Here, we recast much of some of the major lipid and lipoprotein effects of alcohol in the context of this newly discovered G-protein and develop a mechanistic model connecting the interaction of acetate with adipose tissue-GPCR43 with these effects. According to our model, ingestions of acetate could replace alcohol as a means of improving plasma lipid risk factors, improving glucose disposal, and reducing cardiovascular disease. Future studies should include biochemical, cell, animal, and human tests of acetate on energy metabolism. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)
Figures

Open AccessReview PCSK9 Antibodies for the Treatment of Hypercholesterolemia
Nutrients 2014, 6(12), 5517-5533; doi:10.3390/nu6125517
Received: 7 September 2014 / Revised: 24 October 2014 / Accepted: 4 November 2014 / Published: 1 December 2014
Cited by 15 | PDF Full-text (227 KB) | HTML Full-text | XML Full-text
Abstract
The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and
[...] Read more.
The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C) plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145) and alirocumab (REGN727/SAR236553), have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk. Full article
(This article belongs to the Special Issue Lipoprotein Metabolism and Atherosclerosis)

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