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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

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

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 ]
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 ]

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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 

Mgr. Eliška Haasová

PhD Student

Mgr. Veronika Kalendová

PhD Student

Mgr. Marko Mitrović

PhD Student

Mgr. Isaiah Sabinari

PhD Student

Mgr. Nivasini Shekhar

PhD Student

Mgr. Sara Stanić

PhD Student

Mgr. Karolína Seďová

Technician

Daniela Šálková

Technician

Ing. Jitka Vyvadilová

Technician