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- Calabresi, Laura2
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Regular Research Articles
30 Results
- Research ArticleOpen Access
Associations between insulin-like growth factor binding protein-2 and lipoprotein kinetics in men
Journal of Lipid ResearchVol. 63Issue 10100269Published online: August 28, 2022- Chloé Rauzier
- Benoît Lamarche
- André J. Tremblay
- Patrick Couture
- Frédéric Picard
Cited in Scopus: 0Low circulating concentrations of insulin-like growth factor binding protein-2 (IGFBP-2) have been associated with dyslipidemia, notably with high triglyceride (TG) levels. However, the determinants by which IGFBP-2 influences lipoprotein metabolism, especially that of TG-rich lipoproteins (TRLs), are poorly understood. Here, we aimed to assess the relationships between IGFBP-2 levels and lipoprotein production and catabolism in human subjects. Fasting IGFBP-2 concentrations were measured in the plasma of 219 men pooled from previous lipoprotein kinetics studies. - Research ArticleOpen Access
ANGPTL4 silencing via antisense oligonucleotides reduces plasma triglycerides and glucose in mice without causing lymphadenopathy
Journal of Lipid ResearchVol. 63Issue 7100237Published online: June 3, 2022- Mingjuan Deng
- Elda Kutrolli
- Anne Sadewasser
- Sven Michel
- Masoumeh Motamedi Joibari
- Frank Jaschinski
- and others
Cited in Scopus: 1Angiopoietin-like 4 (ANGPTL4) is an important regulator of plasma triglyceride (TG) levels and an attractive pharmacological target for lowering plasma lipids and reducing cardiovascular risk. Here, we aimed to study the efficacy and safety of silencing ANGPTL4 in the livers of mice using hepatocyte-targeting GalNAc-conjugated antisense oligonucleotides (ASOs). Compared with injections with negative control ASO, four injections of two different doses of ANGPTL4 ASO over 2 weeks markedly downregulated ANGPTL4 levels in liver and adipose tissue, which was associated with significantly higher adipose LPL activity and lower plasma TGs in fed and fasted mice, as well as lower plasma glucose levels in fed mice. - Research ArticleOpen Access
Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial
Journal of Lipid ResearchVol. 63Issue 7100233Published online: May 20, 2022- Rene Rodriguez-Gutierrez
- Jose Gerardo González
- Deven Parmar
- Farheen. Shaikh
- Pio Cruz-López
Cited in Scopus: 0Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. - Research ArticleOpen Access
Plasma FA composition in familial LCAT deficiency indicates SOAT2-derived cholesteryl ester formation in humans
Journal of Lipid ResearchVol. 63Issue 7100232Published online: May 18, 2022- Chiara Pavanello
- Alice Ossoli
- Arianna Strazzella
- Patrizia Risè
- Fabrizio Veglia
- Marie Lhomme
- and others
Cited in Scopus: 0Mutations in the LCAT gene cause familial LCAT deficiency (Online Mendelian Inheritance in Man ID: #245900), a very rare metabolic disorder. LCAT is the only enzyme able to esterify cholesterol in plasma, whereas sterol O-acyltransferases 1 and 2 are the enzymes esterifying cellular cholesterol in cells. Despite the complete lack of LCAT activity, patients with familial LCAT deficiency exhibit circulating cholesteryl esters (CEs) in apoB-containing lipoproteins. To analyze the origin of these CEs, we investigated 24 carriers of LCAT deficiency in this observational study. - Research ArticleOpen Access
Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown
Journal of Lipid ResearchVol. 63Issue 6100222Published online: May 7, 2022- Sabrina Sailer
- Katharina Lackner
- Mia L. Pras-Raves
- Eric J.M. Wever
- Jan B. van Klinken
- Adriaan D. Dane
- and others
Cited in Scopus: 0Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations. In addition, manipulation of AGMO in macrophages led to significant changes in the cellular lipidome, and alkylglycerolipids, the preferred substrates of AGMO, were shown to accumulate in mature adipocytes. - Research ArticleOpen Access
Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia
Journal of Lipid ResearchVol. 63Issue 6100209Published online: April 20, 2022- Weilai Dong
- Karen H.Y. Wong
- Youbin Liu
- Michal Levy-Sakin
- Wei-Chien Hung
- Mo Li
- and others
Cited in Scopus: 0Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4–36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. - Research ArticleOpen Access
The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses
Journal of Lipid ResearchVol. 63Issue 6100208Published online: April 14, 2022- Zack Saud
- Victoria J. Tyrrell
- Andreas Zaragkoulias
- Majd B. Protty
- Evelina Statkute
- Anzelika Rubina
- and others
Cited in Scopus: 9The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. - Research ArticleOpen Access
Determination of tissue contributions to the circulating lipid pool in cold exposure via systematic assessment of lipid profiles
Journal of Lipid ResearchVol. 63Issue 7100197Published online: March 14, 2022- Raghav Jain
- Gina Wade
- Irene Ong
- Bhagirath Chaurasia
- Judith Simcox
Cited in Scopus: 1Plasma lipid levels are altered in chronic conditions such as type 2 diabetes and cardiovascular disease as well as during acute stresses such as fasting and cold exposure. Advances in MS-based lipidomics have uncovered a complex plasma lipidome of more than 500 lipids that serve functional roles, including as energy substrates and signaling molecules. This plasma lipid pool is maintained through regulation of tissue production, secretion, and uptake. A major challenge in understanding the lipidome complexity is establishing the tissues of origin and uptake for various plasma lipids, which is valuable for determining lipid functions. - Research ArticleOpen Access
Gut microbiome-derived glycine lipids are diet-dependent modulators of hepatic injury and atherosclerosis
Journal of Lipid ResearchVol. 63Issue 4100192Published online: March 9, 2022- Courtney L. Millar
- Liya Anto
- Chelsea Garcia
- Mi-Bo Kim
- Anisha Jain
- Anthony A. Provatas
- and others
Cited in Scopus: 1Oral and gut Bacteroidetes produce unique classes of serine-glycine lipodipeptides and glycine aminolipids that signal through host Toll-like receptor 2. These glycine lipids have also been detected in human arteries, but their effects on atherosclerosis are unknown. Here, we sought to investigate the bioactivity of bacterial glycine lipids in mouse models of atherosclerosis. Lipid 654 (L654), a serine-glycine lipodipeptide species, was first tested in a high-fat diet (HFD)-fed Ldlr−/− model of atherosclerosis. - Research ArticleOpen Access
The SGLT2 inhibitor dapagliflozin promotes systemic FFA mobilization, enhances hepatic β-oxidation, and induces ketosis
Journal of Lipid ResearchVol. 63Issue 3100176Published online: February 1, 2022- Kristina Wallenius
- Tobias Kroon
- Therese Hagstedt
- Lars Löfgren
- Maria Sörhede-Winzell
- Jeremie Boucher
- and others
Cited in Scopus: 15Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10-3H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (Ra), whole-body FFA oxidation (Rox), and nonoxidative disposal (Rst). - Research ArticleOpen Access
Lipid droplet-mitochondria coupling via perilipin 5 augments respiratory capacity but is dispensable for FA oxidation
Journal of Lipid ResearchVol. 63Issue 3100172Published online: January 20, 2022- Benedikt Kien
- Stephanie Kolleritsch
- Natalia Kunowska
- Christoph Heier
- Gabriel Chalhoub
- Anna Tilp
- and others
Cited in Scopus: 5Disturbances in lipid homeostasis can cause mitochondrial dysfunction and lipotoxicity. Perilipin 5 (PLIN5) decorates intracellular lipid droplets (LDs) in oxidative tissues and controls triacylglycerol (TG) turnover via its interactions with adipose triglyceride lipase and the adipose triglyceride lipase coactivator, comparative gene identification-58. Furthermore, PLIN5 anchors mitochondria to the LD membrane via the outermost part of the carboxyl terminus. However, the role of this LD-mitochondria coupling (LDMC) in cellular energy catabolism is less established. - Research ArticleOpen Access
Apolipoprotein F concentration, activity, and the properties of LDL controlling ApoF activation in hyperlipidemic plasma
Journal of Lipid ResearchVol. 63Issue 2100166Published online: January 7, 2022- Richard E. Morton
- Daniel Mihna
Cited in Scopus: 0Apolipoprotein F (ApoF) modulates lipoprotein metabolism by selectively inhibiting cholesteryl ester transfer protein activity on LDL. This ApoF activity requires that it is bound to LDL. How hyperlipidemia alters total plasma ApoF and its binding to LDL are poorly understood. In this study, total plasma ApoF and LDL-bound ApoF were quantified by ELISA (n = 200). Plasma ApoF was increased 31% in hypercholesterolemic plasma but decreased 20% in hypertriglyceridemia. However, in donors with combined hypercholesterolemia and hypertriglyceridemia, the elevated triglyceride ameliorated the rise in ApoF caused by hypercholesterolemia alone. - Research ArticleOpen Access
Transgelin: a new gene involved in LDL endocytosis identified by a genome-wide CRISPR-Cas9 screen
Journal of Lipid ResearchVol. 63Issue 1100160Published online: December 10, 2021- Diego Lucero
- Ozan Dikilitas
- Michael M. Mendelson
- Zahra Aligabi
- Promotto Islam
- Edward B. Neufeld
- and others
Cited in Scopus: 4A significant proportion of patients with elevated LDL and a clinical presentation of familial hypercholesterolemia do not carry known genetic mutations associated with hypercholesterolemia, such as defects in the LDL receptor. To identify new genes involved in the cellular uptake of LDL, we developed a novel whole-genome clustered regularly interspaced short palindromic repeat-Cas9 KO screen in HepG2 cells. We identified transgelin (TAGLN), an actin-binding protein, as a potentially new gene involved in LDL endocytosis. - Research ArticleOpen Access
Apolipoprotein E content of VLDL limits LPL-mediated triglyceride hydrolysis
Journal of Lipid ResearchVol. 63Issue 1100157Published online: December 1, 2021- Brynne E. Whitacre
- Philip Howles
- Scott Street
- Jamie Morris
- Debi Swertfeger
- W. Sean Davidson
Cited in Scopus: 8High levels of circulating triglycerides (TGs), or hypertriglyceridemia, are key components of metabolic diseases, such as type 2 diabetes, metabolic syndrome, and CVD. As TGs are carried by lipoproteins in plasma, hypertriglyceridemia can result from overproduction or lack of clearance of TG-rich lipoproteins (TRLs) such as VLDLs. The primary driver of TRL clearance is TG hydrolysis mediated by LPL. LPL is regulated by numerous TRL protein components, including the cofactor apolipoprotein C-II, but it is not clear how their effects combine to impact TRL hydrolysis across individuals. - Research ArticleOpen Access
Lipoprotein size is a main determinant for the rate of hydrolysis by exogenous LPL in human plasma
Journal of Lipid ResearchVol. 63Issue 1100144Published online: October 25, 2021- Oleg Kovrov
- Fredrik Landfors
- Valeria Saar-Kovrov
- Ulf Näslund
- Gunilla Olivecrona
Cited in Scopus: 3LPL is a key player in plasma triglyceride metabolism. Consequently, LPL is regulated by several proteins during synthesis, folding, secretion, and transport to its site of action at the luminal side of capillaries, as well as during the catalytic reaction. Some proteins are well known, whereas others have been identified but are still not fully understood. We set out to study the effects of the natural variations in the plasma levels of all known LPL regulators on the activity of purified LPL added to samples of fasted plasma taken from 117 individuals. - Research ArticleOpen Access
The lipid substrate preference of CETP controls the biochemical properties of HDL in fat/cholesterol-fed hamsters
Journal of Lipid ResearchVol. 62100027Published online: January 27, 2021- Richard E. Morton
- Daniel Mihna
- Yan Liu
Cited in Scopus: 0Cholesteryl ester transfer protein (CETP) modulates lipoprotein metabolism by transferring cholesteryl ester (CE) and triglyceride (TG) between lipoproteins. However, differences in the way CETP functions exist across species. Unlike human CETP, hamster CETP prefers TG over CE as a substrate, raising questions regarding how substrate preference may impact lipoprotein metabolism. To understand how altering the CE versus TG substrate specificity of CETP might impact lipoprotein metabolism in humans, we modified CETP expression in fat/cholesterol-fed hamsters, which have a human-like lipoprotein profile. - Research ArticleOpen Access
Vasculoprotective properties of plasma lipoproteins from brown bears (Ursus arctos)
Journal of Lipid ResearchVol. 62100065Published online: March 10, 2021- Matteo Pedrelli
- Paolo Parini
- Jonas Kindberg
- Jon M. Arnemo
- Ingemar Bjorkhem
- Ulrika Aasa
- and others
Cited in Scopus: 0Plasma cholesterol and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than healthy humans. Yet, bears display no signs of early stage atherosclerosis development when adult. To explore this apparent paradox, we analyzed plasma lipoproteins from the same 10 bears in winter (hibernation) and summer using size exclusion chromatography, ultracentrifugation, and electrophoresis. LDL binding to arterial proteoglycans (PGs) and plasma cholesterol efflux capacity (CEC) were also evaluated. - Research ArticleOpen Access
Cannabinoid type 1 receptor inverse agonism attenuates dyslipidemia and atherosclerosis in APOE∗3-Leiden.CETP mice
Journal of Lipid ResearchVol. 62100070Published online: March 22, 2021- Robin van Eenige
- Zhixiong Ying
- Lauren Tambyrajah
- Amanda C.M. Pronk
- Niek Blomberg
- Martin Giera
- and others
Cited in Scopus: 0Pharmacological blockade of the cannabinoid type 1 receptor, a G protein-coupled receptor expressed in the central nervous system and various peripheral tissues, reverses diet-induced obesity and dyslipidemia through the reduction of food intake and altered nutrient partitioning. This strategy is being explored for a number of therapeutic applications; however, its potency for the treatment of atherosclerotic cardiovascular disease via improvements in lipid metabolism remains unclear. Therefore, here, we aimed to investigate whether inhibition of the endocannabinoid system can attenuate atherosclerosis development through improvement of dyslipidemia. - Research ArticleOpen Access
Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease
Journal of Lipid ResearchVol. 62100085Published online: May 5, 2021- Nickolas Auclair
- Alain T. Sané
- Lena Ahmarani
- Nathalie Patey
- Jean-François Beaulieu
- Noel Peretti
- and others
Cited in Scopus: 0Chylomicron retention disease (CRD) is an autosomal recessive disorder associated with biallelic Sar1b mutations leading to defects in intracellular chylomicron (CM) trafficking and secretion. To date, a direct cause-effect relationship between CRD and Sar1b mutation has not been established, but genetically modified animal models provide an opportunity to elucidate unrecognized aspects of these mutations. To examine the physiological role and molecular mechanisms of Sar1b function, we generated mice expressing either a targeted deletion or mutation of human Sar1b using the CRISPR-Cas9 system. - Research ArticleOpen Access
Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4
Journal of Lipid ResearchVol. 62100091Published online: June 9, 2021- Bingxiang Wang
- Yishi Shen
- Lei Zhai
- Xiaodan Xia
- Hong-mei Gu
- Maggie Wang
- and others
Cited in Scopus: 0Plasma LDL is produced from catabolism of VLDL and cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL-C levels. Circulating PCSK9 is mainly secreted by the liver, whereas VLDL is exclusively secreted by hepatocytes. However, the mechanism regulating their secretion is not completely understood. Surfeit 4 (Surf4) is a cargo receptor localized in the ER membrane. It recruits cargos into coat protein complex II vesicles to facilitate their secretion. - Research ArticleOpen Access
Nonalcoholic fatty liver disease stratification by liver lipidomics
Journal of Lipid ResearchVol. 62100104Published online: August 9, 2021- Olga Vvedenskaya
- Tim Daniel Rose
- Oskar Knittelfelder
- Alessandra Palladini
- Judith Andrea Heidrun Wodke
- Kai Schuhmann
- and others
Cited in Scopus: 18Nonalcoholic fatty liver disease (NAFLD) is a common metabolic dysfunction leading to hepatic steatosis. However, NAFLD's global impact on the liver lipidome is poorly understood. Using high-resolution shotgun mass spectrometry, we quantified the molar abundance of 316 species from 22 major lipid classes in liver biopsies of 365 patients, including nonsteatotic patients with normal or excessive weight, patients diagnosed with NAFL (nonalcoholic fatty liver) or NASH (nonalcoholic steatohepatitis), and patients bearing common mutations of NAFLD-related protein factors. - Research ArticleOpen Access
EPA and DHA containing phospholipids have contrasting effects on membrane structure
Journal of Lipid ResearchVol. 62100106Published online: August 12, 2021- Samuel C.R. Sherratt
- Rebecca A. Juliano
- Christina Copland
- Deepak L. Bhatt
- Peter Libby
- R. Preston Mason
Cited in Scopus: 0Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl—Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. - Research ArticleOpen Access
Angiopoietin-like 3 inhibition of endothelial lipase is not modulated by angiopoietin-like 8
Journal of Lipid ResearchVol. 62100112Published online: August 26, 2021- Kelli L. Sylvers-Davie
- Ashley Segura-Roman
- Alicia M. Salvi
- Kylie J. Schache
- Brandon S.J. Davies
Cited in Scopus: 0High plasma triglyceride (TG) levels and low HDL-C levels are risk factors for atherosclerosis and cardiovascular disease. Both plasma TG and HDL-C levels are regulated in part by the circulating inhibitor, angiopoietin-like 3 (ANGPTL3). ANGPTL3 inhibits the phospholipase, endothelial lipase (EL), which hydrolyzes the phospholipids of HDL, thus decreasing plasma HDL levels. ANGPTL3 also inhibits LPL, the lipase primarily responsible for the clearance of TGs from the circulation. Previous studies have shown that ANGPTL3 requires complex formation with the related ANGPTL protein, angiopoietin-like 8 (ANGPTL8), to efficiently inhibit LPL, but the role of ANGPTL8 in EL inhibition is not known. - Research ArticleOpen Access
Inhibition of chylomicron assembly leads to dissociation of hepatic steatosis from inflammation and fibrosis
Journal of Lipid ResearchVol. 62100123Published online: September 23, 2021- Yan Xie
- Elizabeth P. Newberry
- Elizabeth M. Brunt
- Samuel J. Ballentine
- Saeed Soleymanjahi
- Elizabeth A. Molitor
- and others
Cited in Scopus: 0Regulating dietary fat absorption may impact progression of nonalcoholic fatty liver disease (NAFLD). Here, we asked if inducible inhibition of chylomicron assembly, as observed in intestine-specific microsomal triglyceride (TG) transfer protein knockout mice (Mttp-IKO), could retard NAFLD progression and/or reverse established fibrosis in two dietary models. Mttp-IKO mice fed a methionine/choline-deficient (MCD) diet exhibited reduced hepatic TGs, inflammation, and fibrosis, associated with reduced oxidative stress and downstream activation of c-Jun N-terminal kinase and nuclear factor kappa B signaling pathways. - Research ArticleOpen Access
Red blood cell triglycerides—a unique pool that incorporates plasma-free fatty acids and relates to metabolic health
Journal of Lipid ResearchVol. 62100131Published online: October 3, 2021- Yilin Song
- Michael D. Jensen
Cited in Scopus: 0Most research into red blood cell (RBC) lipids focuses on membrane phospholipids and their relationships to metabolic conditions and diet. Triglycerides (TGs) exist in most cells; the TG-fatty acids serve as readily available fuel for oxidative phosphorylation. Because RBCs lack mitochondria, they would not be expected to store fatty acids in TG. We followed up on a previous in vitro study that found FFA can be incorporated into RBC-TG by testing whether intravenously infused [U-13C]palmitate could be detected in RBC-TG.