17,421 results match your criteria vldl secretion


A simplified procedure to trace triglyceride-rich lipoprotein metabolism in vivo.

Physiol Rep 2021 Apr;9(8):e14820

Department of Medicine, Division of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Glycerol tri[ H]oleate and [ C]cholesteryl oleate double-labeled triglyceride-rich lipoprotein (TRL)-like particles are a well-established tool to trace the effect of lipid-modulating interventions on TRL metabolism. The routine generation of these particles involves sonication of a lipid mixture and subsequent fractionation of resulting particles into populations of different average size through density gradient ultracentrifugation. Here, we describe a simplified and more time-efficient procedure for preparing TRL-like particles without the need of fractionation. Read More

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Apolipoprotein C-II and C-III preferably transfer to both high-density lipoprotein (HDL)2 and the larger HDL3 from very low-density lipoprotein (VLDL).

Biol Chem 2021 May 18;402(4):439-449. Epub 2020 Dec 18.

Life Science Research Center, Nagano Children's Hospital, 3100 Toyoshina, Azumino 399-8288, Japan.

Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid homeostasis. During triglyceride lipolysis, the apoCs are known to be transferred from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL), but the detailed mechanisms of this transfer remain unclear. In this study, we investigated the extent of the apoC transfers and their distribution in HDL subfractions, HDL2 and HDL3. Read More

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Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

Sci Rep 2021 Apr 28;11(1):9203. Epub 2021 Apr 28.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Read More

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leaf extract attenuates hepatic lipogenesis and adipogenesis.

Food Funct 2021 Apr 28. Epub 2021 Apr 28.

Department of Life Science, Bokjeong-dong, Sujung-gu, Sungnam-si, Gyeongg-do 461-701, Republic of Korea.

Annona muricata (graviola) is a medicinal plant that can be used to alleviate chronic human diseases by providing antioxidants and inducing immunomodulation. In this study, we found that treatment of AML12 hepatocytes with steam (SGE) and ethanol (EGE) extracts of graviola leaf downregulated the expression of fatty acid (FA) oxidation genes, including ACOX1, CPT1, and PPARα, with no change in the expression of FA synthesis genes. However, whereas EGE inhibited the differentiation and lipid accumulation of 3T3-L1 adipocytes and downregulated FA synthesis genes, no similar changes were observed in response to treatment with SGE. Read More

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Metabolic-associated fatty liver disease and lipoprotein metabolism.

Mol Metab 2021 Apr 20:101238. Epub 2021 Apr 20.

Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Background: Non-alcoholic fatty liver disease, or as recently proposed 'metabolic-associated fatty liver disease' (MAFLD), is characterized by pathological accumulation of triglycerides and other lipids in hepatocytes. This common disease can progress from simple steatosis to steatohepatitis, and eventually end-stage liver diseases. MAFLD is closely related to disturbances in systemic energy metabolism, including insulin resistance and atherogenic dyslipidemia. Read More

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Nutrient infusion in the dorsal vagal complex controls hepatic lipid and glucose metabolism in rats.

iScience 2021 Apr 26;24(4):102366. Epub 2021 Mar 26.

Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Hypothalamic regulation of lipid and glucose homeostasis is emerging, but whether the dorsal vagal complex (DVC) senses nutrients and regulates hepatic nutrient metabolism remains unclear. Here, we found in rats DVC oleic acid infusion suppressed hepatic secretion of triglyceride-rich very-low-density lipoprotein (VLDL-TG), which was disrupted by inhibiting DVC long-chain fatty acyl-CoA synthetase that in parallel disturbed lipid homeostasis during intravenous lipid infusion. DVC glucose infusion elevated local glucose levels similarly as intravenous glucose infusion and suppressed hepatic glucose production. Read More

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Naringin improves lipid metabolism in a tissue-engineered liver model of NAFLD and the underlying mechanisms.

Life Sci 2021 Apr 20;277:119487. Epub 2021 Apr 20.

Difficult & Complicated Liver Diseases and Artificial Liver Center & Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing YouAn Hospital, Capital Medical University, Beijing, China. Electronic address:

Aims: Nonalcoholic fatty liver disease (NAFLD) is a lipid metabolism disorder. Naringin (a main active ingredient in Ganshuang granules) is a flavanone that has been demonstrated to exert hepatoprotective and antifibrotic effects. The present study aimed to use a novel tissue-engineered fatty liver model to assess the effects and mechanisms of naringin on NAFLD. Read More

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High Dietary Intervention of Lauric Triglyceride Might be Harmful to Its Improvement of Cholesterol Metabolism in Obese Rats.

J Agric Food Chem 2021 Apr 12;69(15):4453-4463. Epub 2021 Apr 12.

Jiangxi Province Key Laboratory of Edible and Medicinal Resources Exploitation, School of Resource and Environmental and Chemical Engineering, Nanchang University, Nanchang 330031, China.

Hypercholesterolemia is often considered to be a major risk factor for atherosclerosis, and medium-chain fatty acids have been found to reduce the total cholesterol (TC) level and maintain low-density lipoprotein cholesterol (LDL-c) stability. However, we unexpectedly found that the levels of TC and LDL-c were increased in obese rats treated with high-dose lauric triglycerides (LT). The study aimed to investigate the effect and mechanism of LT on cholesterol metabolism in obese rats. Read More

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Elucidation of the mechanism of NEFA-induced PERK-eIF2α signaling pathway regulation of lipid metabolism in bovine hepatocytes.

J Steroid Biochem Mol Biol 2021 Apr 2;211:105893. Epub 2021 Apr 2.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, PR China. Electronic address:

During the periparturient transition period, negative energy balance (NEB) characterized by high concentrations of non-esterified fatty acids (NEFA) may cause fatty liver and ketosis in dairy cows. Previous studies have shown that the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the endoplasmic reticulum stress (ERS) response plays an important role in lipid metabolism in hepatocytes. This study, therefore, investigated the role of the PERK-branch in NEFA-induced fatty liver. Read More

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Levels of Lipid Parameters in Children with Arterial Ischemic Stroke and Headache: Case-Control Study and Meta-Analysis.

Brain Sci 2021 Mar 26;11(4). Epub 2021 Mar 26.

Department of Pediatric Neurology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, Medykow Str 16, 40-752 Katowice, Poland.

Abnormalities in levels of lipid parameters are one of the main causes of cardiovascular and cerebrovascular disease in adults. There are limited data on the role of disturbances of lipid metabolism in the etiopathogenesis of arterial ischemic stroke (AIS) in children and the results provided are ambiguous. The aim of the study was to compare the levels of lipid parameters (total cholesterol [TC], triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL]) between children with AIS, children with headache and healthy children. Read More

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PCSK9 Levels and Metabolic Profiles in Elderly Subjects with Different Glucose Tolerance under Statin Therapy.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Research Unit of Biomedicine, Medical Research Center, Faculty of Medicine, University of Oulu and Oulu University Hospital, 90014 Oulu, Finland.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Read More

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β-hydroxy-β-methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue.

Biol Sport 2021 Mar 21;38(1):113-121. Epub 2020 Aug 21.

Department of Physical Education, Universidade Federal de Viçosa, MG, Brazil.

The effects of resistance training (RT) associated with calcium β-hydroxyβ-methylbutyrate (CaHMB) supplementation on the body composition and gene expression of cytokines related to skeletal muscle hypertrophy and adipose tissue metabolism were studied in rats. Male Wistar rats were divided into four groups of 12 animals: sedentary control (SC); sedentary supplemented (SS); resistance training control (RTC) and resistance training supplemented (RTS). Rats from RTC and RTS groups were submitted to an RT programme and those from SS and RTS groups received 1 mL of CaHMB (320 mg kg day) by gavage, for 8 weeks. Read More

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Cannabinoid type 1 receptor inverse agonism attenuates dyslipidemia and atherosclerosis in APOE∗3-Leiden.CETP mice.

J Lipid Res 2021 Mar 23;62:100070. Epub 2021 Mar 23.

Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Pharmacological 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. Read More

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The role of increased FGF21 in VLDL-TAG secretion and thermogenic gene expression in mice under protein malnutrition.

Biosci Biotechnol Biochem 2021 Apr;85(5):1104-1113

Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan.

Protein malnutrition promotes hepatic lipid accumulation in growing animals. In these animals, fibroblast growth factor 21 (FGF21) rapidly increases in the liver and circulation and plays a protective role in hepatic lipid accumulation. To investigate the mechanism by which FGF21 protects against liver lipid accumulation under protein malnutrition, we determined whether upregulated FGF21 promotes the thermogenesis or secretion of very-low-density lipoprotein (VLDL)-triacylglycerol (TAG). Read More

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Impaired Very-Low-Density Lipoprotein catabolism links hypoglycemia to hypertriglyceridemia in Glycogen Storage Disease type Ia.

J Inherit Metab Dis 2021 Mar 19. Epub 2021 Mar 19.

Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Prevention of hypertriglyceridemia is one of the biomedical targets in Glycogen Storage Disease type Ia (GSD Ia) patients, yet it is unclear how hypoglycemia links to plasma triglyceride (TG) levels. We analyzed whole-body TG metabolism in normoglycemic (fed) and hypoglycemic (fasted) hepatocyte-specific glucose-6-phosphatase deficient (L-G6pc ) mice. De novo fatty acid synthesis contributed substantially to hepatic TG accumulation in normoglycemic L-G6pc mice. Read More

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Early socialization and environmental enrichment of lactating piglets affects the caecal microbiota and metabolomic response after weaning.

Sci Rep 2021 Mar 17;11(1):6113. Epub 2021 Mar 17.

Animal Nutrition and Welfare Service, Department of Animal and Food Science, Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain.

The aim of this study was to determine the possible impact of early socialization and an enriched neonatal environment to improve adaptation of piglets to weaning. We hypothesized that changes in the microbiota colonization process and in their metabolic response and intestinal functionality could help the animals face weaning stress. A total of 48 sows and their litters were allotted into a control (CTR) or an enriched treatment (ENR), in which piglets from two adjacent pens were combined and enriched with toys. Read More

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Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis.

Cell Rep 2021 Mar;34(11):108873

Mitochondria Biology Laboratory, Brain Research Center, Quebec, QC, Canada; Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Laval University, Quebec, QC, Canada. Electronic address:

Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. Read More

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Plasma cholesterol levels and short-term adaptations of metabolism and milk production during feed restriction in early lactating dairy cows on pasture.

J Anim Physiol Anim Nutr (Berl) 2021 Mar 16. Epub 2021 Mar 16.

Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

Low plasma total cholesterol (TC) concentrations are characteristic during the negative energy balance in early lactating dairy cows. The objective was to investigate short-term effects of different TC concentrations during an aggravated energy deficiency through a 1-week concentrate withdrawal on adaptations of metabolism and milk production. Multiparous Holstein cows (n = 15) were investigated during 3 week beginning at 24 ± 7 DIM (mean ± SD). Read More

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Steatotic hepatocytes release mature VLDL via methionine and tyrosine metabolism in a Keap1-Nrf2 dependent manner.

Hepatology 2021 Mar 16. Epub 2021 Mar 16.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai, 980-8574, Japan.

Nonalcoholic fatty liver disease (NAFLD) is a lipotoxic disease wherein hepatic steatosis and oxidative stress are key pathogenic features. However, whether free amino acids (FAAs) are associated with the oxidative stress response against lipotoxicity has yet to be determined. We hypothesized that an imbalance of FAAs aggravates hepatic steatosis by interfering with the oxidative stress sensor. Read More

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Vasculoprotective Properties of Plasma Lipoproteins from Brown Bears (Ursus arctos).

J Lipid Res 2021 Mar 10:100065. Epub 2021 Mar 10.

Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Translational Science & Experimental Medicine, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Electronic address:

Plasma cholesterol and triglyceride 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 analysed plasma lipoproteins from the same ten bears in winter (hibernation) and in summer using size exclusion chromatography, ultracentrifugation and electrophoresis. Read More

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Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes.

Diabetes Obes Metab 2021 Mar 12. Epub 2021 Mar 12.

Novo Nordisk A/S, Søborg, Denmark.

Aim: To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D).

Materials And Methods: In this randomized, double-blind, single-centre, crossover trial, subjects with T2D received once-daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12-week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat-rich) at the end of each treatment period. Read More

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Dietary phosphatidylcholine supplementation reduces atherosclerosis in Ldlr male mice.

J Nutr Biochem 2021 06 8;92:108617. Epub 2021 Mar 8.

Food and Nutritional Science, Department of Agricultural, University of Alberta, Edmonton, Alberta, Canada; Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Choline is an essential nutrient required for various biological processes. Eggs, dairy, and meat are rich in phosphatidylcholine (PC), whereas cereal and legumes are rich in free choline. Excess dietary choline leads to increase plasma trimethylamine N-oxide (TMAO). Read More

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Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis.

Cardiovasc Res 2021 Mar 8. Epub 2021 Mar 8.

Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.

Aims: Fibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and nonalcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive.

Methods And Results: Here, the role of FGF21 in lipoprotein metabolism in relation to atherosclerosis development was investigated by pharmacological administration of a half-life extended recombinant FGF21 protein to hypercholesterolemic APOE*3-Leiden. Read More

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Hepatocyte-specific Hepatocyte Nuclear Factor 4 alpha (HNF4α) deletion decreases resting energy expenditure by disrupting lipid and carbohydrate homeostasis.

Gene Expr 2021 Mar 10. Epub 2021 Mar 10.

University of Kansas Medical Center - Pharmacology, Toxicology and Therapeutics.

Hepatocyte Nuclear Factor 4 alpha (HNF4α) is required for hepatocyte differentiation and regulates expression of genes involved in lipid and carbohydrate metabolism including those that control VLDL secretion and gluconeogenesis. Whereas previous studies have focused on specific genes regulated by HNF4α in metabolism, its overall role in whole body energy utilization has not been studied. In this study, we used indirect calorimetry to determine the effect of hepatocyte-specific HNF4α deletion (HNF4α-KO) in mice on whole body energy expenditure (EE) and substrate utilization in fed, fasted, and high fat diet (HFD) conditions. Read More

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Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial.

J Hepatol 2021 Mar 6. Epub 2021 Mar 6.

Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland.

Background & Aims: Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake.

Methods: A total of 94 healthy men were studied in this double-blind, randomized trial. Read More

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Palmitic acid-rich oils with and without interesterification lower postprandial lipemia and increase atherogenic lipoproteins compared with a MUFA-rich oil: A randomized controlled trial.

Am J Clin Nutr 2021 Mar 1. Epub 2021 Mar 1.

Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.

Background: Interesterified (IE) fats are widely used in place of trans fats; however, little is known about their metabolism.

Objectives: To test the impact of a commonly consumed IE compared with a non-IE equivalent fat on in vivo postprandial and in vitro lipid metabolism, compared with a reference oil [rapeseed oil (RO)].

Methods: A double-blinded, 3-phase crossover, randomized controlled trial was performed in healthy adults (n = 20) aged 45-75 y. Read More

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Protective effects of the imidazoline-like drug lnp599 in a marmoset model of obesity-induced metabolic disorders.

Int J Obes (Lond) 2021 Mar 2. Epub 2021 Mar 2.

Laboratoire de Pharmacologie et Toxicologie NeuroCardiovasculaire - UR7296, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.

Background/objectives: Overweight and obesity are undoubtable risk factors for type 2 diabetes and cardiovascular diseases and significantly contribute to the global morbi-mortality. We previoulsy reported that LNP599, a pharmacological imidazoline-like activator of hepatic AMPK/adiponectin signaling, protects against the development of adiposity and obesity and the associated cardio-metabolic disorders, suggesting that it may be a suitable drug candidate for a therapeutic approach targeting the development of obesity at very early stages. The objective of the present study was to evaluate the metabolic effects of LNP599 in a model of diet-induced overweight and metabolic disorders in a nonhuman primate, the common marmoset (Callithrix jacchus), and more particularly to establish the impact of the compound on cholesterol homeostasis, i. Read More

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Sex-Dependent Dyslipidemia and Neuro-Humoral Alterations Leading to Further Cardiovascular Risk in Juvenile Obesity.

Front Nutr 2020 12;7:613301. Epub 2021 Feb 12.

Mental Health Department, Santa Casa de São Paulo School of Medical Sciences, São Paulo, Brazil.

Childhood obesity is a growing concern as the World Health Organization (WHO) states that ~10% of adolescents worldwide are overweight or obese. This condition is the reflex of energy imbalance between the calories consumed and those expended. Sex-related responses associated with dyslipidemia, hormonal alterations, and neuro-humoral disruptions in childhood obesity are the focus of the present investigation. Read More

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February 2021

Liver specific deletion of mouse Tm6sf2 promotes steatosis, fibrosis and hepatocellular cancer.

Hepatology 2021 Feb 27. Epub 2021 Feb 27.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, United States.

Background And Aims: Human TM6SF2 variant rs58542926 is associated with nonalcoholic fatty liver disease (NAFLD) and hepatocellular cancer (HCC). However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased VLDL secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD. Read More

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February 2021