Laboratory of Adipose Tissue Biology

Laboratory of Adipose Tissue Biology - bg 3

Content of this page

Laboratory of Adipose Tissue Biology - biologie tukove tkane

About the Laboratory

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)

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

Achievements

In 2018, Ondřej Kuda was awarded the Lumina Quaeruntur praemium for outstanding prospective researchers from the Czech Academy of Sciences.

The Lumina Quaeruntur fellowship was established by the Academy Council of the Czech Academy of Sciences as an instrument to support scientific excellence in the CAS. It is intended to award outstanding prospective researchers in setting up new scientific teams at the research institutes of the CAS to allow developing their science programme focused on conceptually new topics that significantly shift the frontiers of knowledge.

Six award-winning scientists are chosen every year, and Ondřej Kuda was among them in 2018.

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.

The Department of Adipose Tissue Biology is involved in extensive cooperation among excellent European laboratories in order to:

  1. identify markers of healthy development (BIOCLAIMS project; 11 partners);
  2. describe mechanisms which could increase energy expenditure in adipose tissue and prevent fat accumulation in the body (DIABAT project; 20 partners); and
  3. analyze the effect of omega-3 administered as phospholipids from Krill oil on non-alcoholic fatty liver disease (FOIE GRAS project; 10 partners).

Especially the DIABAT project corresponds with the long-term strategy of the Department (see Kopecky J et al. 1995 J. Clin. Invest. 96:2914-2923 and review Flachs P et al. 2013. BBA). All projects involve dietary and/or pharmacological experiments on laboratory mice. To reach to goals of these projects, we use complex in vivo phenotyping of animals (including an indirect calorimetry system, hyperinsulinemic-euglycemic clamps, in vivo analysis of body composition, and various tolerance and behavioral tests), advanced analytical tools (metabolipidomic analysis and gene expression screens), and cell culture studies.

For newer papers see section Publications.

Jan Kopecký, MD, DSc. won a special prize awarded by the Ministry of Education, Youth and Sports for a set of his research group’s papers on the effects of omega-3 fatty acids, published in the last 5 years.

On November 21st, 2013, Minister of Education, Youth and Sports Dalibor Štys presented the 2013 awards for extraordinary achievements in science and innovations, which were supported by the Ministry and published during last 5 years. One of the four special awards was given to Dr. Jan Kopecký of Institute of Physiology, Academy of Sciences of the Czech Republic for the results of the studies focused on “New mechanisms in the complex effects of omega-3 fatty acids: perspectives for health”. Omega-3 fatty acids (omega-3) from sea fish decrease the risk of develoment of diseases linked to obesity and inflammation, namely cardiovascular disease and diabetes. In experiments on mice, Dr. Jan Kopecký together with his colleagues discovered involvement of hormones, anti-inflammatory molecules and other mechanisms in beneficial metabolic effects of omega-3. Based on these results, new therapeutical approaches for treatment of patients with type 2 diabetes are now explored in a collaboration with Diabetes Centre at IKEM, Prague. The award is based on 12 articles published in prominent international scientific journals during 2009–2013.

 

Awarded set of papers:

1) Flachs P, Rossmeisl M , Bryhn M , and Kopecký J. 2009. Cellular and molecular effects of n-3 polyunsaturated fatty acids on adipose tissue biology and metabolism. Clinical Science 116:1-16

2) Rossmeisl M, Jeleník T, Jilková Z, Slamová K, Kůs V, Hensler M, Medříková D, Povyšíl C, Flachs P, Mohamed-Ali V, Bryhn M, Berge K, Holmeide AK, and Kopecký J. 2009. Prevention and reversal of obesity and glucose intolerance in mice by DHA-derivatives. Obesity 17: 1023-1031

3) van Schothorst EM, Flachs P, Franssen-van Hal NL, Kuda O, Bunschoten A, Molthoff J, Vink C, Hooiveld G J, Kopecký J, and Keijer J. 2009. Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet. BMC Genomics 10 :110

4) Kuda O, Jeleník T, Jilková Z, Flachs P, Rossmeisl M, Hensler M, Kazdová L, Ogston N, Baranowski M, Gorski J, Janovská P, Kůs V, Polák J, Mohamed-Ali V, Burcelin R, Cinti S, Bryhn M, and Kopecký J. 2009. n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia 52 :941-51

5) Kuda O, Stankova B, Tvrzicka E, Hensler M, Jelenik T, Rossmeisl M, Flachs P, Kopecky J. 2009. Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet. Journal of Physiology and Pharmacology 60: 135-140

6) Kopecký J, Rossmeisl M, Flachs P, Kuda O, Jilková Z, Staňková B, Tvrzická E, and Bryhn M. 2009. n-3 polyunsaturated fatty acids: bioavailability and modulation of adipose tissue function. Proc Nutr Soc 68: 361-369

7) Jeleník T, Rossmeisl M, Kuda O, Macek Jilková Z, Medřiková D, Kůs V, Hensler M, Janovská P, Mikšík I, Baranowski M, Gorski J, Hébrard S, Jensen TE, Flachs P, Hawley S, Viollet B, and Kopecký J. 2010. AMPK-activated protein kinase alpha 2 subunit is required for the preservation of hepatic insulin sensitivity by n-3 polyunsaturated fatty acids. Diabetes 59:2737-2746

8) Flachs P, Rühl R, Hensler M, Janovská P, Zouhar P, Kůs V, Macek Jilková Z, Papp E, Kuda O, Svobodová M, Rossmeisl M, Tsenov G, Mohamed-Ali V, and Kopecký J. 2011. Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids. Diabetologia 54: 2626-2683

9) Kůs V, Flachs P, Kuda O, Bardová K, Janovská P, Svobodová M, Macek Jilková Z, Rossmeisl M, Wang-Sattler R, Yu Z, Illig T, and Kopecký J. 2011. Unmasking differential effects of rosiglitazone and pioglitazone in the combination treatment with n-3 fatty acids in mice fed a high-fat diet. PLoS ONE  6(11):e27126

10) Horáková O, Medříková D, van Schothorst EM, Bunschoten A, Flachs P, Kůs V, Kuda O, Bardová K, Janovská P, Hensler M, Rossmeisl M, Wang-Sattler R, Prehn C, Adamski J, Illig T, Keijer J, and Kopecký J. 2012. Preservation of metabolic flexibility in skeletal muscle by a combined use of n-3 PUFA and rosiglitazone in dietary obese mice. PLoS ONE 7(8):e43764

11) Flachs P, Rossmeis M, Kuda O, and Kopecký J. 2013. Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: A key to lean phenotype BBA – Molecular and Cell Biology of Lipids. Biochim Biophys Acta. 1831(5):986-1003.

12) Macek Jilkova Z, Hensler M, Medrikova D, Janovska P, Horakova O, Rossmeisl M, Flachs P, Sell H, Eckel J and Kopecký J. 2013. Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice. Int J Obes. 1-8, Epub 2013 July 2.

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.

Comment to papers awarded in year 2009

Mechanisms, by which omega-3 polyunsaturated fatty acids (omega-3) from sea fish ameliorate health problems associated with excessive accumulation of body fat, are systematically studied at the Department of Adipose Tissue Biology of the Institute of Physiology AS CR. In the experiments on mice, the authors demonstrated that dietary intake of omega-3 results in: 1) a partial protection against obesity induced by high-fat diet; 2) induction of mitochondria and lipid oxidation specifically in adipose tissue and small intestine, while reducing ectopic fat deposition in other tissues and lipotoxicity; 3) induction of the release of insulin-sensitizing hormone adiponectin from adipose tissue. New chemical derivatives of n-3 PUFA were developed, which exert strong antidiabetic efects. In spite of the fact that omega-3 could not affect insulin resistance in diabetic patients, it was discovered, that omega-3 augment efficacy of thiazolidinediones (TZD), drugs improving insulin sensitivity in diabetic patients. Only the combination treatment reduced accumulation of body fat. The improvement in insulin sensitivity reflected synergistic effects of omega-3 and TZD on muscle glucose metabolism. The combination treatment by n-3 PUFA and TZD may allow for reducing both the dose requirements and cost of the TZD therapy, and it may also reduce the incidence of adverse side-effects of the therapy. The new treatment is already tested at the Centre of Diabetology at the Institute for Clinical and Experimental Medicine in Prague. Most of the research was performed in collaboration with companies in Norway (i.e., the PronovaBiopharma a.s., Lysaker; and more recently with EPAX a.s., Aaalesund). These results were listed among other the most important scientific achievements of the CAS – see the Annual Report of the CAS for 2009.

Comment to paper awarded in year 2011

The effects of combination treatment using omega-3 and mild calorie restriction were characterized on the model of dietary-obese mice fed by high fat diet. Replacement of 10% dietary lipids by omega-3 together with 10% calorie restriction prevent weight gain and insulin resistance, despite the fact that omega-3 or calorie restriction alone cannot counteract induction of obesity. Combination treatment reduced significantly whole-body inflammation, which is connected to obesity. The crucial consequences of the combination treatment were metabolic changes in adipose tissue and production of anti-inflammatory lipid mediators. The results are important for development of novel strategies in prevention and treatment of obesity and diabetes, eventually other disorders related to chronic inflammation, such as some neurodegenerative and gastrointestinal diseases. (Flachs P et al. 2011. Diabetologia 54:2626-38)

Comment to paper awarded in year 2017

The effects of cold exposure (6 °C for 2 or 7 days) on adipose tissue metabolism were compared in obesity prone C57BL/6J and obesity-resistant A/J mice. The main novel results were that triacylglycerol/fatty acid cycling and de novo lipogenesis in adipose tissue, as well as hepatic lipoprotein production, are integrated to provide energy fuels for thermogenesis and thus could contribute to lean phenotype. The results are important for understanding the mechanisms underlying obesity development. (Flachs et al., Int J Obes (Lond) 41: 372-380)

Among the five most cited recent publications of Institute of Physiology are repeatedly three papers of our department.

These are the following:

Flachs P., Mohamed-Ali V., Horaková O., Rossmeisl M., Hosseinzadeh-Attar M.J., Hensler M., Růžičková J., Kopecký J. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia. 2006 Feb;49(2):394-7. 245 citations by 3/2020

Flachs P., Horaková O., Brauner P., Rossmeisl M., Pecina P., Franssen-van Hal N., Růžičková J., Šponarová J., Drahota Z., Vlček Č., Keijer J., Houstek J. , Kopecký J. Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia. 2005 Nov;48(11):2365-75. 239 citations by 3/2020

Růžičková J., Rossmeisl M., Pražák T., Flachs P., Šponarová J., Vecka M., Tvrzická E., Bryhn M., Kopecký J. Omega-3 PUFA of marine origin limit diet-induced obesity in mice by reducing cellularity of adipose tissue. Lipids. 2004 Dec;39(12):1177-85. 200 citations by 3/2020

Otto Wichterle Award for outstanding young scientists of the Czech Academy of Sciences was awarded to Pavel Flachs (2009) and Ondřej Kuda (2014) from our department.

The Otto Wichterle Award is presented anually by the Czech Academy of Sciences to stimulate and encourage selected, exceptionally outstanding, promising young scientists from the Czech Academy of Sciences for their remarkable contributions to the advancement of scientific knowledge in a given area of science. Nominees with scientific degrees (CSc., Dr., Ph.D., DrSc.) are eligible if they are not over 35 years of age in the calendar year in which the nominations are submitted.

Ten award-winning scientists are chosen every year in the area of life and chemical sciences. Pavel Flachs was among them in 2009, Ondřej Kuda in 2014.

Publications

Vagnerová; Karla - Hudcovic; Tomáš - Vodička; Martin - Ergang; Peter - Klusoňová; Petra - Hermanová; Petra - Šrůtková; Dagmar - Pácha; Jiří The effect of oral butyrate on colonic short-chain fatty acid transporters and receptors depends on microbial status. Frontiers in Pharmacology. 2024; 15(Mar 26); 1341333.

IF = 4.4

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

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

Vagnerová; Karla - Gazárková; T. - Vodička; Martin - Ergang; Peter - Klusoňová; Petra - Hudcovic; Tomáš - Šrůtková; Dagmar - Hermanová; Petra - Nováková; L. - Pácha; Jiří Microbiota modulates the steroid response to acute immune stress in male mice. Frontiers in Immunology. 2024; 15(Feb 1); 1330094.

IF = 7.3

Jágr; M. - Hofinger-Horvath; B. - Ergang; Peter - Čepková Hlásná; P. - Schönlechner; R. - Pichler; E. Ch. - DAmico; S. - Grausgruber; H. - Vagnerová; Karla - Dvořáček; V. Comprehensive study of the effect of oat grain germination on the content of avenanthramides. Food Chemistry. 2024; 437(Part 1 30 March); 137807.

IF = 8.8

Stanić; Sara - Bardová; Kristina - Janovská; Petra - Rossmeisl; Martin - Kopecký; Jan - Zouhar; Petr Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling. Biochemical Pharmacology. 2024; 221(March); 116042.

IF = 5.8

People

Head of Laboratory

Vedoucí oddělení
Tel: 3706
Email: martin.rossmeisl@fgu.cas.cz

Deputy Head of Laboratory

Director, Deputy Manager lab. 017
Institute director since 2015
Tel: 2217
Email: Jan.Kopecky@fgu.cas.cz

Laboratory staff

Vědecký pracovník
Tel: 3707
Email: kristina.bardova@fgu.cas.cz
Ošetřovatelka laboratorních zvířat
Tel: 2296
Email: jitka.ezrova@fgu.cas.cz
Tel: 3705
Email: eliska.haasova@fgu.cas.cz
Vědecký pracovník
Tel: 3706
Email: olga.horakova@fgu.cas.cz
Vědecký pracovník
Tel: 3705
Email: petra.janovska@fgu.cas.cz
Tel: 3708
Email: Veronika.kleinova@fgu.cas.cz
Postdoktorand
Tel: 2554
Email: gulnaz.koken@fgu.cas.cz
Koordinátorka
Tel: 3705
Email: zuzana.korandova@fgu.cas.cz
Tel: 3708
Email: marko.mitrovic@fgu.cas.cz
Research Assistant
Tel: 3705
Email: sakina.poonawala@fgu.cas.cz
Doktorand
Tel: 2708
Email: isaiah.sabinari@fgu.cas.cz
Laborantka
Tel: 3704
Email: daniela.salkova@fgu.cas.cz
Odborný pracovník VaV
Tel: 3703
Email: Karolina.Sedova@fgu.cas.cz
Tel: 3705
Email: nivasini.shekhar@fgu.cas.cz
Doktorand
Tel: 3708
Email: sara.stanic@fgu.cas.cz
Email: lenka.steinermrazova@fgu.cas.cz
Magisterský student
Tel: 3705
Email: anna.vavrova@fgu.cas.cz
Vědecký asistent
Tel: 3707
Email: petr.zouhar@fgu.cas.cz