Laboratory of Adipose Tissue Biology

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.

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.

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)

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.