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Triglyceride-Rich Lipoproteins

Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Johan G Schnitzler, Geesje M Dallinga-Thie, Jeffrey Kroon
Over the last century, many studies have demonstrated that low-density lipoprotein (LDL) is a key risk factor of cardiovascular diseases (CVD) related to atherosclerosis. Thus, for these CVD patients, LDL lowering agents are commonly used in the clinic to reduce the risk for CVD. LDL, upon modification, will develop distinct inflammatory and pro-atherogenic potential, leading to impaired endothelial behavior and subsequent increased foam cell formation. LDL can also directly affect circulating monocyte composition, rendering them in a more favorable position to migrate and accumulate in the subendothelial space...
March 16, 2018: Current Medicinal Chemistry
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Stefania Lamon-Fava, Margaret R Diffenderfer, P Hugh R Barrett, Wing Yee Wan, Borbala Postfai, Chorthip Nartsupha, Gregory G Dolnikowski, Ernst J Schaefer
The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B-containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo-controlled, randomized, double-blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4-week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride-rich lipoproteins (TRL), intermediate-density lipoproteins (IDL) and low -density lipoprotein (LDL) and of apo B48 in TRL...
March 14, 2018: Lipids
Vajihe Izadi, Fahimeh Haghighatdoost, Parisa Moosavian, Leila Azadbakht
BACKGROUND: There are no investigations regarding the effects of consuming low-energy-dense diets rich in multiple functional foods on weight-loss maintenance, inflammatory markers, and cardiovascular disease (CVD) risk factors simultaneously. METHOD: This randomized controlled trial design was conducted on 90 men and women who were under a previous weight loss diet. Three months of intervention with recruitment at Allzahra Hospital, Isfahan, Iran, was done. Intervention was conducted following achieving 7-11 kg weight loss...
March 12, 2018: Journal of the American College of Nutrition
Hidekatsu Yanai, Yoshinori Masui, Hisayuki Katsuyama, Hiroki Adachi, Akiko Kawaguchi, Mariko Hakoshima, Yoko Waragai, Tadanao Harigae, Akahito Sako
An epidemiological survey in the Northwest Greenland reported that the Greenlanders have a lower frequency of acute myocardial infarction and diabetes mellitus. The very low incidence of ischemic heart disease in the Greenlanders was explained by consumption of a diet rich in omega-3 polyunsaturated fatty acids (PUFAs). Possible anti-atherothrombotic effects of omega-3 PUFA include an improvement of lipid metabolism such as a reduction of triglyceride and an increase of high-density lipoprotein-cholesterol (HDL-C), and glucose metabolism, anti-platelet activity, anti-inflammatory effects, an improvement of endothelial function and stabilization of atherosclerotic plaque...
April 2018: Journal of Clinical Medicine Research
Helena Vaverková, David Karásek
Familial combined hyperlipidemia (FCH) is the most frequent genetic dyslipidemia (DLP) with high risk of early atherosclerosis manifestation. It is characterized by elevated both triglycerides 1.5 mmol/l and apolipoprotein B 1.2 g/l (hyper-TG/hyper-ApoB fenotype), with at least two affected family members. Despite the fact that plasmatic levels of total cholesterol and LDL-C are usually lower than in familial hypercholesterolemia and full expression of DLP in FCH occurs in adulthood, risk of premature manifestation of atherosclerosis is similar in both these familial DLP...
2018: Vnitr̆ní Lékar̆ství
EunSeok Cha, Sudeshna Paul, Betty J Braxter, Guillermo Umpierrez, Melissa Spezia Faulkner
Purpose The purpose of the study was to examine the associations between dietary behaviors and glucose metabolism in high-risk young adults to increase the precision of nutrition education to prevent early onset type 2 diabetes (T2D). Method Using a descriptive, cross-sectional study design, 106 overweight or obese sedentary young adults ages 18-29 years from the Atlanta metropolitan area were recruited to screen diabetes risk. Survey questionnaires, anthropometric assessment, blood pressure (BP), and laboratory data were collected in a clinical research unit...
March 1, 2018: Diabetes Educator
Michel P Hermans, Paul Valensi
PURPOSE OF REVIEW: The aim of this review is to describe in diabetic patients the determinants underlying atherogenic dyslipidemia, a complex dyslipidemia defined as the coexistence of fasting hypertriglyceridemia and low high-density lipoprotein cholesterol level. Atherogenic dyslipidemia is often comorbid with hyperglycemia in patients with the common form of type 2 diabetes mellitus (T2DM), namely that associated with obesity, insulin resistance, hyperinsulinemia and the metabolic syndrome phenotype...
April 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Katsuyuki Nakajima, Akira Tanaka
PURPOSE OF REVIEW: Oxidized low-density lipoprotein (Ox-LDL) and chylomicron remnants were previously proposed as the most atherogenic lipoproteins for the causal lipoproteins of atherosclerosis. However, there are still controversies on these hypothesizes. Therefore, we have proposed a new hypothesis based on our recent findings of remnant lipoproteins (RLPs) in postprandial plasma. RECENT FINDINGS: Plasma RLP-C and RLP-TG increased significantly after fat load...
April 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Julio A Lamprea-Montealegre, Robyn L McClelland, Morgan Grams, Pamela Ouyang, Moyses Szklo, Ian H de Boer
OBJECTIVE: This study sought to characterise the main dyslipidaemic phenotypes present in chronic kidney disease (CKD) and their association with coronary heart disease (CHD) risk. METHODS: Analyses included 6612 individuals in the multiethnic study of atherosclerosis free of CHD at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) of 15 to <60 mL/min/1.73 m2 (stages 3-4). Principal component analyses were used to characterise the main dyslipidaemic phenotypes of CKD accounting for the correlation among different lipoproteins and lipoprotein particles...
February 22, 2018: Heart: Official Journal of the British Cardiac Society
Bimit Mahat, Étienne Chassé, Clare Lindon, Jean-François Mauger, Pascal Imbeault
Circulating fatty acids are a major systemic energy source in the fasting state as well as a determinant of hepatic triglyceride (TG)-rich very low-density lipoprotein (VLDL) production. Upon acute hypoxia, sympathetic arousal induces adipose tissue lipolysis, resulting in an increase in circulating non-esterified fatty acids (NEFA). Animal studies suggest that TG clearance may also be strongly reduced under hypoxia, though this effect has been shown to be dependent on temperature. Whether the hypoxia-induced rise in blood fatty acid concentrations effects fasting TG levels in humans under thermoneutral conditions remains unknown...
February 21, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Ping-Ping He, Ting Jiang, Xin-Ping OuYang, Ya-Qin Liang, Jie-Qiong Zou, Yan Wang, Qian-Qian Shen, Li Liao, Xi-Long Zheng
Lipoprotein lipase (LPL) is a rate-limiting enzyme that catalyzes hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins including chylomicrons (CM), low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL). A variety of parenchymal cells can synthesize and secrete LPL. Recent studies have demonstrated that complicated processes are involved in LPL biosynthesis, secretion and transport. The enzyme activity of LPL is regulated by many factors, such as apolipoproteins, angiopoietins, hormones and miRNAs...
February 14, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Mikael Larsson, Christopher M Allan, Patrick J Heizer, Yiping Tu, Norma P Sandoval, Rachel S Jung, Rosemary L Walzem, Anne P Beigneux, Stephen G Young, Loren G Fong
GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the subendothelial spaces and transports it to the capillary lumen. In Gpihbp1-/- mice, LPL remains stranded in the subendothelial spaces, causing hypertriglyceridemia, but how Gpihbp1-/- mice respond to metabolic stress (e.g., cold exposure) has never been studied. In wild-type mice, cold exposure increases LPL-mediated processing of triglyceride-rich lipoproteins (TRLs) in brown adipose tissue (BAT), providing fuel for thermogenesis and leading to lower plasma triglyceride levels...
February 15, 2018: Journal of Lipid Research
Erin E Mulvihill
PURPOSE OF REVIEW: The intestine is highly efficient at absorbing and packaging dietary lipids onto the structural protein apoB48 for distribution throughout the body. Here, we summarize recent advances into understanding the physiological and pharmacological actions of the proglucagon-derived peptides: glucagon like peptide 1 (GLP-1) and glucagon like peptide 2 (GLP-2) on intestinal lipoprotein secretion. RECENT FINDINGS: Several recent studies have elucidated mechanisms underlying the paradoxical effects of GLP-1 and GLP-2 on intestinal production of triglyceride-rich lipoproteins (TRLs)...
February 9, 2018: Current Opinion in Lipidology
Andrea Baragetti, Daniela Grejtakova, Manuela Casula, Elena Olmastroni, Gloria Saccani Jotti, Giuseppe Danilo Norata, Alberico L Catapano, Stefano Bellosta
After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants...
February 8, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Li Wang, Benhua Zeng, Zhiwei Liu, Zhenlin Liao, Qingping Zhong, Lihui Gu, Hong Wei, Xiang Fang
There is an increasing interest in the effect of dietary polyphenols on the intestinal microbiota and the possible associations between this effect and the development of obesity. However, limited information is available on how these polyphenols affect the gut microbiota and lipid metabolism. The co-action of a high-fat diet (HFD) and tea polyphenol (TP) on gut microbiota and lipid metabolism using a human flora-associated (HFA) C57BL/6J mice model is studied. TP reduced serum total cholesterol, triglyceride, low density lipoprotein, glucose (GLU) and insulin (INS) levels of HFD mice in a dose-dependent manner (P < 0...
March 2018: Journal of Food Science
Theodosios D Filippatos, Angelos Liontos, Eliza C Christopoulou, Moses S Elisaf
Over the last 3 decades, hypolipidaemic treatment has significantly reduced both cardiovascular (CV) risk and events, with statins being the cornerstone of this achievement. Nevertheless, residual CV risk and unmet goals in hypolipidaemic treatment make novel options necessary. Recently marketed monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown the way towards innovation, while other ways of PCSK9 inhibition like small interfering RNA (Inclisiran) are already being tested...
February 8, 2018: Current Vascular Pharmacology
Ira J Goldberg
Cholesterol is not the only lipid that causes heart disease. Triglyceride supplies the heart and skeletal muscles with highly efficient fuel and allows for the storage of excess calories in adipose tissue. Failure to transport, acquire, and use triglyceride leads to energy deficiency and even death. However, overabundance of triglyceride can damage and impair tissues. Circulating lipoprotein-associated triglycerides are lipolyzed by lipoprotein lipase (LpL) and hepatic triglyceride lipase. We inhibited these enzymes and showed that LpL inhibition reduces high-density lipoprotein cholesterol by >50%, and hepatic triglyceride lipase inhibition shifts low-density lipoprotein to larger, more buoyant particles...
February 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Børge G Nordestgaard, Stephen J Nicholls, Anne Langsted, Kausik K Ray, Anne Tybjærg-Hansen
New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9)...
February 8, 2018: Nature Reviews. Cardiology
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