A5041468944- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Lipoproteins and Cardiovascular Health
- Cancer-related molecular mechanisms research
- Lipid metabolism and biosynthesis
- Atherosclerosis and Cardiovascular Diseases
- Cholesterol and Lipid Metabolism
- Renin-Angiotensin System Studies
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Liver Disease Diagnosis and Treatment
- Caveolin-1 and cellular processes
- Cancer, Hypoxia, and Metabolism
- Anesthesia and Pain Management
- T-cell and B-cell Immunology
- Cardiovascular Disease and Adiposity
- Diabetes and associated disorders
- Restless Legs Syndrome Research
- Intraoperative Neuromonitoring and Anesthetic Effects
- Fibroblast Growth Factor Research
- Pancreatic function and diabetes
Umeå University
2014-2024
Lipigon Pharmaceuticals (Sweden)
2022-2024
University Hospital of Umeå
2024
Universität Hamburg
2016-2020
University Medical Center Hamburg-Eppendorf
2016-2018
Tallinn University of Technology
2007
Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define role FOXP3-expressing Tregs in atherosclerosis, we used DEREG mouse, which expresses diphtheria toxin (DT) receptor under control Treg-specific Foxp3 promoter, allowing for specific ablation FOXP3+ Tregs. Lethally irradiated,...
Enhanced TGF-β signaling may promote plaque stability and prevent clinical manifestations of atherosclerosis.
Abstract Brown and beige adipocytes combust nutrients for thermogenesis through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic affects metabolism anti-atherogenic properties high-density (HDL) is unknown. Here, we report a reduction atherosclerosis response to pharmacological stimulation linked increased HDL levels APOE*3-Leiden.CETP Both cold-induced enhances remodelling, which associated with...
Apolipoprotein A-V (apoA-V) is present in low amounts plasma and has been found to modulate triacylglycerol levels humans animal models. ApoA-V displays affinity for members of the density lipoprotein receptor (LDL-R) gene family, known as classical receptors, including LRP1 SorLA/LR11. In addition LDL-A binding repeats, mosaic SorLA/LR11 also possesses a Vps10p domain. Here we show that apoA-V binds sortilin, from Vsp10p domain family lacks repeats. Binding sortilin was competed by...
Apolipoprotein A-V is a potent modulator of plasma triacylglycerol levels. To investigate the molecular basis for this phenomenon we explored ability apolipoprotein A-V, in most experiments complexed to disks dimyristoylphosphatidylcholine, interact with two members low density lipoprotein receptor family, receptor-related protein and mosaic type-1 receptor, SorLA. Experiments using surface plasmon resonance showed specific binding both free lipid-bound receptors. The was calcium dependent...
Abstract Background Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoproteins and makes fatty acids available for tissue metabolism. The activity of the enzyme is modulated a specific manner by interaction with other proteins. We have studied how feeding/fasting some related perturbations affect expression, rat adipose tissue, three such proteins, LMF1, an ER protein necessary folding LPL into its active dimeric form, endogenous inhibitor ANGPTL4, GPIHBP1, that transfers across...
Significance Insulin resistance and β-cell failure are the major defects in type 2 diabetes. We now demonstrate that local insulin resistance-induced increase apolipoprotein CIII (apoCIII) within pancreatic islets causes promotion of an intraislet inflammatory milieu, increased mitochondrial metabolism, deranged regulation cytoplasmic free Ca 2+ concentration ([Ca ] i ), apoptosis. Decreasing apoCIII vivo animals with improves glucose tolerance, knockout transplanted into diabetic mice, high...
Abstract Aims APOC3, ANGPTL3, and ANGPTL4 are circulating proteins that actively pursued as pharmacological targets to treat dyslipidaemia reduce the risk of atherosclerotic cardiovascular disease. Here, we used human genetic data compare predicted therapeutic adverse effects inactivation. Methods results We conducted drug-target Mendelian randomization analyses using variants in proximity genes associated with protein levels drug targets. obtained exposure outcome from large-scale...
Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting LPL in trans Golgi network has not, hitherto, been understood detail. Here, we characterize role SorLA (officially known as SorLA-1 or sortilin-related receptor) intracellular trafficking LPL. We found that bound to under neutral acidic conditions, cells this binding mainly occurred vesicular structures. expression changed subcellular distribution so it became more concentrated...
In 1976, Fasano, et al., described a new technique of posterior rhizotomy for treatment spasticity. They stimulated electrically fascicles the roots in spastic patients and found that some responded to stimulation with tonic muscle contractions. cut these fascicles, preserving those weaker or no reaction. The present authors have used fairly similar eight spasticity legs one patient arm: all T12-Sl C6-8, respectively, were during surgery under general anesthesia. Approximately 60% 80% jerks,...
Excess body fat is a major health issue and risk factor for the development of numerous chronic diseases. Low-carbohydrate diets like Atkins Diet are popular rapid weight loss, but long-term consequences remain subject debate. The Scandinavian low-carbohydrate high-fat (LCHF) diet, which has been in countries about decade, very low carbohydrate content (~5 E %) rich includes high proportion saturated fatty acids. Here we investigated metabolic physiological diet with macronutrient...
During the diagnosis of three unrelated patients with severe hypertriglyceridemia, APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which result in hypertriglyceridemia remain poorly understood, functional impairment/s induced these specific was not obvious. Therefore, we performed a thorough structural analysis that included follow-up their closest relatives,...
Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid remains incompletely understood.We evaluated herein triglyceride-derived incorporation into adipose tissue depots, LPL mass and activity, mRNA levels content proteins involved activity transport, expression/activity enzymes...
Angiopoietin-like 4 (ANGPTL4) is an important regulator of plasma triglyceride (TG) levels and attractive pharmacological target for lowering lipids reducing cardiovascular risk. Here, we aimed to study the efficacy safety silencing ANGPTL4 in livers mice using hepatocyte-targeting GalNAc-conjugated antisense oligonucleotides (ASOs). Compared with injections negative control ASO, four two different doses ASO over 2 weeks markedly downregulated liver adipose tissue, which was associated...
Abstract Background and Aims Angiopoietin-like 3 (ANGPTL3) 4 (ANGPTL4) inhibit lipoprotein lipase to regulate tissue fatty acid uptake from triglyceride-rich lipoproteins such as VLDL. While pharmacological inhibition of ANGPTL3 is being evaluated lipid-lowering strategy, systemic ANGPTL4 not pursued due adverse effects. This study aimed compare the therapeutic potential liver-specific Angptl3 Angptl4 silencing attenuate hyperlipidemia atherosclerosis development in APOE*3-Leiden.CETP mice,...
Apolipoprotein CII (apoCII), a surface constituent of plasma lipoproteins, is the activator for lipoprotein lipase (LPL) and therefore central lipid transport in blood. The three-dimensional structure 13C-, 15N-enriched human full-length apoCII complex with sodium dodecyl sulfate (SDS) micelles reported. In addition to determination, 15N-relaxation measurements have been performed at two magnetic fields characterize dynamics backbone complex. relaxation data also provided global structural...
Objective Determination of the in vivo significance LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development absence its main ligand apoE. Methods Results LRP1 knock-in mice carrying an inactivating mutation NPxYxxL motif were crossed with apoE-deficient mice. In apoE, relative to wild-type animals, mutated showed increased clearance postprandial lipids despite a compromised endocytosis rate inefficient insulin-mediated translocation receptor...
Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice investigated the importance of function lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used analyze expression hearts wild-type Lrig3-deficient mice. In addition, molecular,...