A5038041556- Lipid metabolism and disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- Diabetes and associated disorders
- Ion channel regulation and function
- Lipid metabolism and biosynthesis
- Multiple Sclerosis Research Studies
- Plant nutrient uptake and metabolism
- Plant Stress Responses and Tolerance
- Congenital heart defects research
- Chromosomal and Genetic Variations
- Physiological and biochemical adaptations
- Nuclear and radioactivity studies
- Peptidase Inhibition and Analysis
- Enhanced Oil Recovery Techniques
- Cancer, Lipids, and Metabolism
- Fish Ecology and Management Studies
- Aquaculture Nutrition and Growth
- Fluid Dynamics and Mixing
- Metabolism and Genetic Disorders
- Science, Research, and Medicine
- Genomic variations and chromosomal abnormalities
- Radiopharmaceutical Chemistry and Applications
- Ubiquitin and proteasome pathways
Rigshospitalet
2000-2025
University of Copenhagen
2011-2025
Copenhagen University Hospital
2023-2025
Glostrup Hospital
2011
Regionshospitalet Herning
2005
Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of LPL, key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member the ANGPTL family, ANGPTL3, to act on LPL. much like ANGPTL4, physiologically relevant regulator LPL activity, which causes irreversible inactivation enzyme. Here, we show can form complexes with either ANGPTL3 or ANGPTL4 when proteins are refolded together from their denatured states. In contrast augmented inhibitory...
Lipoprotein lipase (LPL) undergoes spontaneous inactivation via global unfolding and this is prevented by GPIHBP1 (Mysling et al., 2016). We now show: (1) that ANGPTL4 inactivates LPL catalyzing the of its hydrolase domain; (2) binding to renders largely refractory inhibition; (3) both LU domain intrinsically disordered acidic are required for protective effect. Genetic studies have found a common polymorphic variant in results lower plasma triglyceride levels. report: less efficient LPL;...
GPIHBP1 is a glycolipid-anchored membrane protein of capillary endothelial cells that binds lipoprotein lipase (LPL) within the interstitial space and shuttles it to lumen. The LPL•GPIHBP1 complex responsible for margination triglyceride-rich lipoproteins along capillaries their lipolytic processing. current work conceptualizes model GPIHBP1•LPL interaction based on biophysical measurements with hydrogen-deuterium exchange/mass spectrometry, surface plasmon resonance, zero-length...
Movement of lipoprotein lipase (LPL) from myocytes or adipocytes to the capillary lumen is essential for intravascular lipolysis and plasma triglyceride homeostasis—low LPL activity in causes hypertriglyceridemia. The trans-endothelial transport depends on ionic interactions with GPIHBP1's intrinsically disordered N-terminal tail, which harbors two acidic clusters at positions 5–12 19–30. This polyanionic tail provides a molecular switch that controls detachment heparan sulfate proteoglycans...
Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures have remained elusive. Inspired by our recent discovery that GPIHBP1's preserves structure activity, we crystallized...
The binding of lipoprotein lipase (LPL) to GPIHBP1 focuses the intravascular hydrolysis triglyceride-rich lipoproteins on surface capillary endothelial cells. This process provides essential lipid nutrients for vital tissues (e.g., heart, skeletal muscle, and adipose tissue). Deficiencies in either LPL or impair triglyceride hydrolysis, resulting severe hypertriglyceridemia. activity is regulated by angiopoietin-like proteins 3, 4, 8 (ANGPTL). Dogma has held that these ANGPTLs inactivate...
Significance Dietary fats absorbed by intestinal enterocytes are packaged into chylomicrons, which circulate in the bloodstream until docking along capillary endothelial cells, primarily striated muscle and adipose tissue. There, a functional unit composed of lipoprotein lipase (LPL) GPIHBP1 hydrolyzes triglycerides releasing free fatty acids for use surrounding parenchymal cells. The current study describes interactions between LPL how disordered region results order stability within LPL....
The complex between lipoprotein lipase (LPL) and its endothelial receptor (GPIHBP1) is responsible for the lipolytic processing of triglyceride-rich lipoproteins (TRLs) along capillary lumen, a physiologic process that releases lipid nutrients vital organs such as heart skeletal muscle. LPL activity regulated in tissue-specific manner by endogenous inhibitors (angiopoietin-like [ANGPTL] proteins 3, 4, 8), but molecular mechanisms are incompletely understood. ANGPTL4 catalyzes inactivation...
The lipolytic processing of triglyceride-rich lipoproteins (TRLs) by lipoprotein lipase (LPL) is crucial for the delivery dietary lipids to heart, skeletal muscle, and adipose tissue. TRLs LPL regulated in a tissue-specific manner complex interplay between activators inhibitors. Angiopoietin-like protein 4 (ANGPTL4) inhibits reducing its thermal stability catalyzing irreversible unfolding LPL's α/β-hydrolase domain. We previously mapped ANGPTL4 binding site on defined downstream events...
GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) transports across ECs to its site of action in capillary lumen. GPIHBP1's 3-fingered LU domain required for LPL binding, but function acidic (AD) has remained unclear. We created mutant mice lacking AD found severe hypertriglyceridemia. As expected, GPIHBP1 retained capacity bind LPL. Unexpectedly, however, most was located on abluminal...
A chromosomal deletion syndrome associated with a 22q13 microdeletion has previously been reported in approximately 75 children. We report six cases from Denmark of 22q13. One was cytogenetically visible by conventional karyotyping, one diagnosed high resolution karyotyping after the demonstration low arylsulfatase activity. Two were CGH analysis, multisubtelomeric FISH analysis and serendipitously as lack control signal for 22q11 deletion. mosaic 16% cells showing two signals. The phenotype...
Calmodulin (CaM) engages in Ca 2+ -dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction the human Na + /H -exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, fibroblasts stably expressing wildtype mutant NHE1, we discovered multiple accessible states of this functionally important complex existing different NHE1:CaM stoichiometries structures. We determined NMR solution...
Two sterols of the cholesterol biosynthetic pathway induce resumption meiosis in mouse oocytes vitro. The sterols, termed meiosis-activating (MAS), have been isolated from human follicular fluid (FF-MAS, 4,4-dimethyl-5 alpha-cholest-8,14,24-triene-3 beta-ol) and bull testicular tissue (T-MAS, alpha-cholest-8,24-diene-3 beta-ol). FF-MAS is first intermediate biosynthesis lanosterol converted to T-MAS by sterol delta 14-reductase. An inhibitor 7-reductase 14 reductase, AY9944-A-7, causes cells...
Tau protein has been proposed as biomarker of axonal damage leading to irreversible neurological impairment in MS. CSF concentrations may be useful when determining risk progression from ON MS.To investigate the association between tau concentration and 14-3-3 cerebrospinal fluid (CSF) patients with monosymptomatic optic neuritis (ON) versus onset who progressed multiple sclerosis (MS). To evaluate results against data found a complete literature review.A total 66 MS and/or Department...
LPL is essential for intravascular lipid metabolism and of high medical relevance. Since notoriously unstable, there an unmet need a robust expression system producing quantities active pure recombinant human (hLPL). We showed previously that bovine purified from milk unstable at body temperature (Tm 34.8°C), but in the presence endothelial transporter glycosylphosphatidylinositol-anchored density lipoprotein-binding protein 1 (GPIHBP1), stabile increases to 57.6°C). Building on this...
ABSTRACT In euryhaline teleosts the transmural salt and water flow concentration changes along gut were simulated by analogue computation. The purpose was to elucidate interaction of sensitivity parameters system particularly with respect intestinal absorption. simulations based on data obtained from yellow European eel, rainbow trout cyprinodont Aphanius dispar. When experimental values for drinking rate, maximal NaCl absorption rate at half-maximal osmotic permeability coefficient,...