Lipo-Group Research Constellation (LGRC) at Labmed
The final goal of our research activity is the discovery of biomarkers and therapeutic targets for the diagnosis and treatment of cardiometabolic diseases by increasing the knowledge on lipoprotein, lipid, and carbohydrate metabolism.
Cardiometabolic diseases (atherosclerotic cardiovascular disease, diabetes mellitus type II, and non-alcoholic fatty liver disease) are the first cause of mortality and hospitalization worldwide. Epidemiological studies have shown the complexity of cardiometabolic diseases identifying a large number of risk factors.
The liver is a fundamental organ for the regulation of lipoprotein, lipid, and carbohydrate metabolism, being the centre of the physiologic processes that maintain carbohydrate and lipid homeostasis.
The Lipo-Group Research Constellation (LGRC), led by Paolo Parini, Mats Eriksson and Uwe Tietge, merges the efforts and background from various medical specialties (internal medicine, hepatology, gastroenterology, and endocrinology) with the science from genetics, clinical biochemistry, and molecular biology.
The multi-disciplinary expertise and the deep knowledge of human physiology allow LGRC to drive translational pre-clinical and clinical research activities and to integrated the results into models and hypotheses that are translatable to human condition.
Examples of research projects within LGRC
HUMAN (Health and the Understanding of Metabolism, Aging and Nutrition, http://www.fp7human.eu) is a consortium with a EU-funded research project that started in October 2013. HUMAN aims to study the function of genetic risk variant associated to metabolic diseases by employing a unique translational model of human glucose and lipid metabolism: mouse with humanised liver and pancreas. Paolo Parini is the coordinator of HUMAN, and with several member of the LGRC actively contribute with a research activity aimed to: 1) characterize the metabolic phenotype of the humanized mice produced within the consortium, specifically by determining whether the liver humanized mouse model recreates the metabolic characteristics of a human liver and by characterizing changes in clinical metabolic parameters of disease and aging; 2) investigate sex related differences in hepatic lipid and lipoprotein metabolism of the liver humanized mice by repopulation of male or female animals with hepatocytes from disease-free women or men; 3) investigate the humanized phenotype of liver-targeted pharmacology, using the oxysterol receptor LXR as a model system; 4) use CRISPR/Cas9 to genetically modify iPSCs carrying risk/protective alleles.
Professor Uwe Tietge is the newest member of LGRC and brings an additional layer of knowledge. The general theme of his research is to elucidate the molecular regulation of cardiometabolic disease with a focus on (chole)sterol metabolism. As other research projects within LGRC this work is multidisciplinary, extending beyond the physiology of metabolism to a number of relevant biological processes such as inflammation, regeneration and ageing as well as their related outcomes such as atherosclerosis. Central to Tietge’s research are the relevance for human disease and the in vivo aspect, mostly comprising characterization of physiological processes with the help of mouse models. This translational work tests concepts generated in animal models also in human patients or take a vice versa approach to understand the mechanistic basis of clinical observations with the help of animal or cell culture models. Specifically, the following topics are the current focus his work: 1) HDL function and regulation of reverse cholesterol transport; 2) Epigenetic programming of metabolic and cardiovascular health; 3) Impact of the intestinal microbiota on inflammation, bile acid metabolism and cardiometabolic disease including the use of germ-free models.
LGRC also offers a unique competence and technological platform to drive studies for: a) pharmacological target validation, b) evaluation of lipid and glucose metabolism, c) detailed characterization of lipoprotein composition, structure and functions.
Please contact us for more information and possible future collaborations.
Research group leaders
CRISPR Cas9 gene editing, Lipoproteins isolation and characterization (i.e. D2O-sucrose and KBr gradient ultracentrifugation, native and denatured polyacrylamide gel electrophoresis, size exclusion chromatography, serum and HDL cholesterol efflux capacity measurement, lipoprotein binding to arterial proteoglycans), extraction and quantification of lipids and glycogen in cells and tissues, RNA-DNA extraction and purification, enzymatic and ELISA assays, gene expression, protein expression, cloning, mutagenesis, cell culture, transfections.
Work with animal models: quantification of macrophagic reverse cholesterol transport (RCT) in- vivo, glucose and insulin tolerance test, evaluation of atherosclerosis development in the aorta, mouse genotyping, tissue and organ collection, gavage, tail vein injection
EU Fp7 HUMAN (www.fp7human.eu), Swedish Heart-Lung foundation, AstraZeneca, Swedish Research Council, ALF, SSMF, Moderna
BMA undergraduate program, postgraduate courses, medical program, bachelor programs in Biomedicine and Nutrition
The Association of Lipoprotein(a) Plasma Levels With Prevalence of Cardiovascular Disease and Metabolic Control Status in Patients With Type 1 Diabetes.
Littmann K, Wodaje T, Alvarsson M, Bottai M, Eriksson M, Parini P, et al
Diabetes Care 2020 Aug;43(8):1851-1858
New insights from liver-humanized mice on cholesterol lipoprotein metabolism and LXR-agonist pharmacodynamics in humans.
Minniti ME, Pedrelli M, Vedin LL, Delbès AS, Denis RGP, Öörni K, et al
Hepatology 2019 Nov;():
Generation of new hepatocyte-like in vitro models better resembling human lipid metabolism.
Pramfalk C, Jakobsson T, Verzijl CRC, Minniti ME, Obensa C, Ripamonti F, et al
Biochim Biophys Acta Mol Cell Biol Lipids 2020 Jun;1865(6):158659
Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.
Saliba-Gustafsson P, Pedrelli M, Gertow K, Werngren O, Janas V, Pourteymour S, et al
J. Intern. Med. 2019 12;286(6):660-675
The PPAR pan-agonist tetradecylthioacetic acid promotes redistribution of plasma cholesterol towards large HDL.
Lundåsen T, Pedrelli M, Bjørndal B, Rozell B, Kuiper RV, Burri L, et al
PLoS ONE 2020 ;15(3):e0229322
Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα.
Liang N, Damdimopoulos A, Goñi S, Huang Z, Vedin LL, Jakobsson T, et al
Nat Commun 2019 04;10(1):1684
Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice.
Dimova LG, de Boer JF, Plantinga J, Plösch T, Hoekstra M, Verkade HJ, et al
Gastroenterology 2017 08;153(2):382-385.e3
Biliary sterol secretion is required for functional in vivo reverse cholesterol transport in mice.
Nijstad N, Gautier T, Briand F, Rader DJ, Tietge UJ
Gastroenterology 2011 Mar;140(3):1043-51
Culturing of HepG2 cells with human serum improve their functionality and suitability in studies of lipid metabolism.
Pramfalk C, Larsson L, Härdfeldt J, Eriksson M, Parini P
Biochim. Biophys. Acta 2016 Jan;1861(1):51-59