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Laboratory of Adipose Tissue Biology

Laboratory of Adipose Tissue Biology

The Laboratory of Adipose Tissue Biology (Laboratory) is studying physiological regulations of metabolisms and their disturbances in obesity and associated diseases (i.e. Metabolic syndrome). In order to help treat these disorders we explore the influence of drugs, diet and natural substances, namely n-3 polyunsaturated fatty acids of marine origin (omega-3). Our results show the importance of the metabolism of adipose tissue for accumulation of body fat and reveal new possibilities in the prevention and treatment of metabolic disorders linked to obesity by modulating adipose tissue metabolism. We investigate mechanisms that regulate metabolism in health and disease by combining experiments on mice and cell models with clinical studies, and we try to apply new knowledge in clinical medicine. We also focus on ontogenetic development of the studied mechanisms. While working with the manufacturers of the tested substances in the Czech Republic and Norway, we investigate the possible use of omega-3 to increase the effect of drugs and other substances in the treatment of selected diseases. Research projects of the Laboratory reflect the current grant support and the existence of research units established at the Laboratory during 2015. All the mentioned laboratories are closely collaborating and are engaged in translational research conducted in collaboration with clinical as well as industrial partners.

The Energy Metabolism Unit (PI: J. Kopecký) is focused on two complementary areas (i) systemic effects of intrinsic metabolism of white adipose tissue (WAT), and (ii) developmental aspects of energy metabolism and perinatal development in general. With respect to the WAT metabolism, we aim to understand the importance of a "futile" cycle involving the triglyceride hydrolysis and re-esterification of fatty acids (triglyceride/fatty acid cycling) in adipocytes of WAT for resistance to obesity and associated metabolic disorders, namely in the context of calorie restriction, omega-3 administration and cold exposure. The influence of the above manipulations on the formation of lipid mediators, mitochondrial metabolism and proliferation of cells in the adipose tissue is also being characterized. We also focus on the role of epicardial WAT metabolism in heart failure and assocciated cachexia in human patients. Regarding the developmental studies, we focus on the control of postnatal changes in muscle energy metabolism and its significance to obesity in mice, and we characterize perinatal changes in transcriptome of WAT, muscle and liver using a unique biobank of autopsy samples collected from human fetuses and newborns. 

Core members (without workers on maternity leave): P. Janovska, K. Bardova, P. Zouhar, E. Haasova, N. Shekhar, S. Stanic, D. Salkova.

The Glucose Homeostasis Unit (PI: M. Rossmeisl), investigates the mechanisms associated with the effect of dietary lipids on metabolism, with a special focus on omega-3 fatty acids and different lipid forms of their administration. Specifically, we study the changes in ectopic lipid accumulation, glucose metabolism and insulin sensitivity in response to dietary supplementation with omega-3 using various mouse models of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD). We also focus on insulin-sensitizing effects of omega-3 administered as triacylglycerols, phospholipids (Krill oil) or wax esters (Calanus oil), which are studied at the whole-body as well as organ level (muscle, adipose tissue, liver) using in vivo technique of hyperinsulinemic-euglycemic clamps. Collaboration with our Laboratory's Metabolomics Unit (now an independent laboratory, see below) allows us to study the effects of omega-3 supplementation on lipidome, with a particular focus on endocannabinoids. Translational potential regarding the beneficial effects of omega-3 on metabolism is also tested using the transgenic mice expressing the human version of the transcription factor PPARalpha. Relatively recently, we have also begun to address changes in intestinal metabolism in the context of the administration of omega-3 or drugs (e.g., metformin). We also examined changes in intestinal metabolism associated with omega-3 or drug (e.g. metformin) administration. More recently, in collaboration with the 3rd Faculty of Medicine, we have been involved in studies aimed at understanding the role of adipose tissue in the beneficial metabolic effects of exercise, including the role of lipokines secreted by adipose tissue, such as Fatty Acyl esters of Hydroxy Fatty Acids (FAHFAs), particularly those of the PAHSA family. 

Core members (without workers on maternity leaf): O. Horakova, V. Kalendova, M. Mitrovic, I. Sabinari, K. Sedova, J. Vyvadilova.

Until 2019, also the Metabolomics Unit (PI: O. Kuda) formed a part of the Laboratory. However, this research unit became an independent Laboratory of Metabolism of Bioactive Lipids at the Institute, based on the "Lumina Queruntur praemium", a prestigious prize awarded by the Czech Academy of Sciences to O. Kuda. 

Projects

Role of UCP1-independent non-shivering thermogenesis in cold- and obesity-resistance

Regulation of energy expenditure is important for maintanace of stable body temperature and body weight, thus representing potential target for prevention and treatment of obesity and associated disorders. Classical thermogenic mechanisms involve muscle shivering  and UCP1-dependent non-shivering thermogenesis in brown fat. This project is focused on less understood mechanisms of non-shivering thermogenesis, which are independent of UCP1. More

Changes of transcriptome during early postnatal development in humans: impact of premature birth on control of energy metabolism

Premature birth and its complications are the number one cause of death among children under 5 years of age and could impose long-term developmental and health problems. To improve the prognosis of premature newborns, it is necessary to understand the causes of their insufficient postnatal adaptation that depends on the changes in energy metabolism and other mechanisms. However, this research is limited by the lack of clinical materials.  More

Novel approaches to enhance insulin-sensitizing effects of exercise: targeting PAHSA metabolism (ETAPA)

Exercise represents an important tool in the prevention and treatment of metabolic disorders associated with obesity and aging. Metabolic effects of exercise also rely on the induction of favorable changes in adipose tissue function. Adipose tissue is a source of lipokines from the family of palmitic acid esters of hydroxyl fatty acids (PAHSA), which have anti-inflammatory and insulin-sensitizing properties. We have recently shown that 4 months of exercise training increases PAHSA levels in adipose tissue and circulation. However, the mechanisms involved in the induction of PAHSA levels in response to exercise are unknown. More

Physiological relevance of white adipose tissue plasticity and its relationship to the development of obesity and to thermogenic response (closed project)

Sufficient plasticity of white adipose tissue allows to adjust appropriately various metabolic processes in response to changing environmental conditions. Metabolic plasticity of adipose tissue is linked with changes in the size and content of cells within the tissue. A hypothesis will be verified that adipose tissue plasticity, namely the proliferative potential of adipose tissue cells, represents an important factor counteracting toxic effects of fatty acids that are released during the breakdown of lipid stores. Reduced ability of the organism to activate these processes could contribute to the  development of obesity and its metabolic consequences. More

The role of intestine in the metabolic effects of dietary supplementation with omega-3 fatty acids (concluded project)

Dietary supplementation with Omega-3 such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may protect against obesity while exerting hypolipidemic and anti-inflammatory effects. While the effects of omega-3 on lipid metabolism in the liver are relatively well known, changes in intestinal metabolism due to omega-3 administration have not yet been explored in detail. Our previous studies showed that metabolic effects are stronger when omega-3 are administered as phospholipids (Rossmeisl et al., PlosOne 2012). The main goal of this project is to identify the nature of metabolic effects of omega-3 administered in different lipid forms (triacylglycerols, phospholipids, wax esters), mainly with regard to the possible involvement of the intestine in these effects.   More

The role of the endocannabinoid system in metabolic effects of marine omega-3 phospholipids (concluded project)

Metabolic disturbances in obesity are associated with dysregulation of the endocannabinoid (EC) system. We have shown in mice fed an obesogenic high-fat diet that metabolic effects of long-chain omega-3 fatty acids were stronger when supplied in the phospholipid form (omega-3 PL) as compared with triacylglycerols (Rossmeisl et al. 2012. PloS One). These effects were associated with a more efficient modulation of major EC molecules in white adipose tissue (WAT). More

The effect of exercise training and omega-3 supplementation on metabolic parameters and lipidome in elderly women (concluded project)

In the elderly, lifestyle interventions based on the increased physical activity are primarily aimed to improve muscle function and/or cardiovascular fitness, but recent data suggest that adipose tissue may also contribute to the beneficial effects of exercise on metabolism, inflammation and overall health. Wax esters, contained in Calanus oil, is one of the new lipid forms of Omega-3, which may exert improved efficacy in terms of metabolic effects. Therefore, the aim of this project is to study in sedentary older women the effects of exercise training alone or in combination with Calanus oil supplementation. More

Achievements

Our laboratory as a partner in EU projects

Our laboratory has been a partner in EU projects supported through Cooperation program of the European Community (FP7 and H2020) – BIOCLAMS (2010–2015), DIABAT (2011–2015), and FOIE GRAS. More

Our articles repeatedly on the list of the most significant results of Czech Academy of Sciences

Set of our papers regarding novel possibilities of the use of sea fish lipids for prevention and treatment of obesity and associated disorders was included on the list of most significant results of Czech Academy of Sciences in 2009. Our later article dedicated to the combination of omega-3 and mild calorie restriction was included on the same list in 2011. Furthermore, our results describing the changes in adipose tissue metabolism during cold exposure and their relevance to susceptibility to obesity were listed among the best achievements of the Czech Academy of Sciences in 2017.    More

Publications

von Essen; G. - Lindsund; E. - Maldonado; E.M. - Zouhar; Petr - Cannon; B. - Nedergaard; J. Highly recruited brown adipose tissue does not in itself protect against obesity . Molecular Metabolism. 2023; 76(October); 101782 . IF = 8.1 [ASEP] [ doi ]
Picó; C. - Lurbe; E. - Keijer; J. - Kopecký; Jan - Landrier; J.F. - Álvarez-Pitti; J. - Martin; J. Ch. - Oliver; P. - Palou; A. - Palou; M. - Zouhar; Petr - Ribot; J. - Rodrígues; A. M. - Sánchez; J. - Serra; F. - Bonet; M. L. Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv) . Frontiers in Pediatrics. 2023; 11(12 Sep); 1250731 . IF = 2.6 [ASEP] [ doi ]
Janovská; Petra - Zouhar; Petr - Bardová; Kristina - Otáhal; Jakub - Vrbacký; Marek - Mráček; Tomáš - Adamcová; Kateřina - Leňková; Lucie - Funda; Jiří - Čajka; Tomáš - Drahota; Zdeněk - Stanić; Sara - Rustan; A. C. - Horáková; Olga - Houštěk; Josef - Rossmeisl; Martin - Kopecký; Jan . Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle . Molecular Metabolism. 2023; 69(March)); 101683 . IF = 8.1 [ASEP] [ doi ]
Horáková; Olga - Sistilli; Gabriella - Kalendová; Veronika - Bardová; Kristina - Mitrović; Marko - Čajka; Tomáš - Irodenko; Ilaria - Janovská; Petra - Lackner; K. - Kopecký; Jan - Rossmeisl; Martin . Thermoneutral housing promotes hepatic steatosis in standard diet-fed C57BL/6N mice; with a less pronounced effect on NAFLD progression upon high-fat feeding . Frontiers in Endocrinology. 2023; 14(Jul 12); 1205703 . IF = 5.2 [ASEP] [ doi ]
Castillo; P. - Kuda; Ondřej - Kopecký; Jan - Pomar; C. A. - Palou; A. - Palou; M. - Picó; C. Stachydrine; iN/i-acetylornithine and trimethylamine N-oxide levels as candidate milk biomarkers of maternal consumption of an obesogenic diet during lactation . Biofactors. 2023; 49(5); 1022-1037 . IF = 6.0 [ASEP] [ doi ]
Beňová; Andrea - Ferenčáková; Michaela - Bardová; Kristina - Funda; Jiří - Procházka; Jan - Špoutil; František - Čajka; Tomáš - Džubanová; Martina - Balcaen; T. - Kerckhofs; G. - Willekens; W. - van Lenthe; G. H. - Charyyeva; Arzuv - Alquicer; Glenda - Pecinová; Alena - Mráček; Tomáš - Horáková; Olga - Coupeau; Roman - Hansen; M. S. - Rossmeisl; Martin - Kopecký; Jan - Tencerová; Michaela . Omega-3 PUFAs prevent bone impairment and bone marrow adiposity in mouse model of obesity . Communications Biology. 2023; 6(1); 1043 . IF = 5.9 [ASEP] [ doi ]
Oeckl; J. - Janovská; Petra - Adamcová; Kateřina - Bardová; Kristina - Brunner; S. - Dieckmann; S. - Ecker; J. - Fromme; T. - Funda; Jiří - Gantert; T. - Giansanti; P. - Soledad Hidrobo; M. - Kuda; Ondřej - Kuster; B. - Li; Y. - Pohl; Radek - Schmitt; S. - Schweizer; S. - Zischka; H. - Zouhar; Petr - Kopecký; Jan - Klingenspor; M. Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat . Molecular Metabolism. 2022; 61(July)); 101499 . IF = 8.1 [ASEP] [ doi ]
Mitrović; Marko - Sistilli; Gabriella - Horáková; Olga - Rossmeisl; Martin . Omega-3 phospholipids and obesity-associated NAFLD: Potential mechanisms and therapeutic perspectives . European Journal of Clinical Investigation. 2022; 52(3)); e13650 . IF = 5.5 [ASEP] [ doi ]
Funda; Jiří - Villena; J. A. - Bardová; Kristina - Adamcová; Kateřina - Irodenko; Ilaria - Flachs; Pavel - Jedličková; I. - Haasová; Eliška - Rossmeisl; Martin - Kopecký; Jan - Janovská; Petra . Adipose tissue-specific ablation of PGC-1 beta impairs thermogenesis in brown fat . Disease Models & Mechanisms. 2022; 15(4)); dmm049223 . IF = 4.3 [ASEP] [ doi ]
Fisk; H. L. - Childs; C. E. - Miles; E. A. - Ayres; R. - Noakes; P. S. - Paras-Chavez; C. - Kuda; Ondřej - Kopecký; Jan - Antoun; E. - Lillycrop; K. A. - Calder; P. C. Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind; randomised clinical trial . EBioMedicine. 2022; 77(Mar)); 103909 . IF = 11.1 [ASEP] [ doi ]
Castillo; P. - Kuda; Ondřej - Kopecký; Jan - Pomar; C. A. - Palou; A. - Palou; M. - Picó; C. Reverting to a Healthy Diet during Lactation Normalizes Maternal Milk Lipid Content of Diet-Induced Obese Rats and Prevents Early Alterations in the Plasma Lipidome of the Offspring . Molecular Nutrition & Food Research. 2022; 66(17)); 2200204 . IF = 5.2 [ASEP] [ doi ]
Beňová; Andrea - Ferenčáková; Michaela - Bardová; Kristina - Funda; Jiří - Procházka; Jan - Špoutil; František - Čajka; Tomáš - Džubanová; Martina - Balcaen; T. - Kerckhofs; G. - Willekens; W. - van Lenthe; G. H. - Alquicer; Glenda - Pecinová; Alena - Mráček; Tomáš - Horáková; Olga - Rossmeisl; Martin - Kopecký; Jan - Tencerová; Michaela . Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones . Molecular Metabolism. 2022; 65(Nov)); 101598 . IF = 8.1 [ASEP] [ doi ]
Zouhar; Petr - Janovská; Petra - Stanić; Sara - Bardová; Kristina - Funda; Jiří - Haberlová; Blanka - Andersen; B. - Rossmeisl; Martin - Cannon; B. - Kopecký; Jan - Nedergaard; J. A pyrexic effect of FGF21 independent of energy expenditure and UCP1 . Molecular Metabolism. 2021; 53(Nov)); 101324 . IF = 8.568 [ASEP] [ doi ]
Sistilli; Gabriella - Kalendová; Veronika - Čajka; Tomáš - Irodenko; Ilaria - Bardová; Kristina - Oseeva; Marina - Žáček; P. - Kroupová; Petra - Horáková; Olga - Lackner; K. - Gastaldelli; A. - Kuda; Ondřej - Kopecký; Jan - Rossmeisl; Martin . Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity . Nutrients. 2021; 13(2)); 437 . IF = 6.706 [ASEP] [ doi ]
Pražienková; V. - Funda; Jiří - Pirník; Z. - Karnošová; A. - Hrubá; L. - Kořínková; L. - Neprašová; B. - Janovská; Petra - Bencze; Michal - Kadlecová; Michaela - Blahoš; J. - Kopecký; Jan - Železná; B. - Kuneš; Jaroslav - Bardová; Kristina - Maletínská; L. GPR10 gene deletion in mice increases basal neuronal activity; disturbs insulin sensitivity and alters lipid homeostasis . Gene. 2021; 774(Mar 30)); 145427 . IF = 3.913 [ASEP] [ doi ]
Lopes; Magno Alves - Brejchová; Kristýna - Riečan; Martin - Nováková; Michaela - Rossmeisl; Martin - Čajka; Tomáš - Kuda; Ondřej . Metabolomics atlas of oral 13C-glucose tolerance test in mice . Cell Reports. 2021; 37(2)); 109833 . IF = 9.995 [ASEP] [ doi ]
Fisk; H. L. - Childs; C. E. - Miles; E. A. - Ayres; R. - Noakes; P. S. - Paras-Chaves; C. - Kuda; Ondřej - Kopecký; Jan - Antoun; E. - Lillycrop; K. A. - Calder; P. C. Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids . Clinical science. 2021; 135(1); 185-200 . IF = 6.876 [ASEP] [ doi ]
Zouhar; Petr - Rakipovski; G. - Bokhari; M. H. - Busby; O. - Paulsson; J. F. - Conde-Frieboes; K. W. - Fels; J. J. - Raun; K. - Andersen; B. - Cannon; B. - Nedergaard; J. UCP1-independent glucose-lowering effect of leptin in type 1 diabetes: only in conditions of hypoleptinemia . AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM. 2020; 318(1); E72-E76 . IF = 4.310 [ASEP] [ doi ]
Rossmeisl; Martin - Pavlišová; Jana - Bardová; Kristina - Kalendová; Veronika - Burešová; Jana - Kuda; Ondřej - Kroupová; Petra - Staňková; B. - Tvrzická; E. - Fišerová; E. - Horáková; Olga - Kopecký; Jan . Increased plasma levels of palmitoleic acid may contribute to beneficial effects of Krill oil on glucose homeostasis in dietary obese mice . Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. 2020; 1865(8)); 158732 . IF = 4.698 [ASEP] [ doi ]
Pomar; C. A. - Kuda; Ondřej - Kopecký; Jan - Rombaldová; Martina - Castro; H. - Picó; C. - Sánchez; J. - Palou; A. Maternal diet; rather than obesity itself; has a main influence on milk triacylglycerol profile in dietary obese rats . Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. 2020; 1865(2)); 158556 . IF = 4.698 [ASEP] [ doi ]

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People

MUDr. Martin Rossmeisl, Ph.D.

Head of the Laboratory

MUDr. Jan Kopecký, DrSc.

Deputy Head of the Laboratory

Mgr. Olga Horáková, Ph.D.

Senior Researcher

Ing. Petra Janovská, Ph.D.

Senior Researcher

Mgr. Kristina Bardová, Ph.D.

Junior Researcher 

RNDr. Petr Zouhar, Ph.D.

Junior Researcher 

Gülnaz Yıldırım Köken, Ph.D.

Postdoc

Mgr. Eliška Haasová

PhD Student

Mgr. Veronika Kleinová

PhD Student

Mgr. Marko Mitrović

PhD Student

Sakina Poonawala, MSc

PhD student

Mgr. Isaiah Sabinari

PhD Student

Mgr. Sara Stanić

PhD Student

Mgr. Zuzana Korandová

Coordinator

Ing. Jitka Ezrová

Technician

Mgr. Karolína Seďová

Technician

Daniela Šálková

Technician

Ing. Karla Vagnerová, Ph.D.

Lab manager