Intranet Čeština

Adipose Tissue Biology

Adipose Tissue Biology

Our department 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. 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 department reflect the current grant support and the existence of Research laboratories established during 2015.

The "Energy metabolism laboratory" (PI: J. Kopecký) examines the importance of a "futile" cycle involving the triglyceride hydrolysis and re-esterification of fatty acids in adipocytes of white adipose tissue 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. Core members: K. Bardova, P. Janovska, J. Hansikova, S. Hornova.

The "Metabolomics laboratory" (PI: O. Kuda) focuses on the analysis of lipid mediators (eicosanoids, docosanoids) in adipose tissue using the UPLC-MS / MS method, in particular to identify the source of production of various mediators and their effect on metabolism and inflammatory properties of adipose tissue cells (i.e. adipocytes vs. macrophages). Currently, the lab is exploring new anti-diabetic lipids, fatty acid esters of hydroxy fatty acids (FAHFA). New metabolomic methods are also being developed. Core members: M. Brezinova, M. Oseeva, M. Rombaldova, D. Salkova.

The "Glucose homeostasis laboratory" (PI: M. Rossmeisl), by using the method of hyperinsulinemic-euglycemic clamps, analyzes the insulin-sensitizing effects of omega-3 depending on the lipid form (i.e. triacylglycerols vs. phospholipids) of their administration, as well as the involvement of the endocannabinoid system in these effects. We examine the changes in the intestine and their involvement in differential effects of various lipid forms of omega-3 on the whole-body metabolism. Translational potential regarding the beneficial effects of omega-3 on metabolism will also be tested using the transgenic mice expressing the human version of the transcription factor PPARalpha. Core members: O. Horakova, V. Kalendova, P. Kroupová, K. Sedova

All the above mentioned laboratories are closely collaborating and are engaged in translational research conducted in collaboration with clinical as well as industrial partners.

 

 

The Department is subdivided into three laboratories with complementary focus, which closely collaborate and are engaged in translational research conducted together with clinical as well as industrial partners.

 

Projects

Anti-inflammatory effects of novel lipokines of fatty acid esters of hydroxy fatty acids (FAHFA) family in obesity

White adipose tissue (WAT) is a complex endocrine organ and its low-grade inflammation in obesity contributes to the development of metabolic disorders. In 2014, a class of WAT-born lipid mediators - fatty acid esters of hydroxy fatty acids (FAHFA) was discovered [1]. FAHFAs are endogenous lipids with anti-inflammatory and anti-diabetic properties, including the enhancement of glucose tolerance, and insulin and glucagon-like peptide 1 (GLP-1) secretion while reducing inflammatory responses [1-5]. They consist of a fatty acid (e.g. palmitic acid, PA) esterified to the hydroxyl group of a hydroxy fatty acid (e.g. hydroxystearic acid, HSA), abbreviated as PAHSA. The position of the branching carbon defines a regioisomer (e.g. 5-PAHSA). There are several regioisomer families derived from palmitic, palmitoleic, stearic, oleic, linoleic, and docosahexaenoic acid with tissue-specific distribution documented so far [1-4, 6, 7]. Adipose tissue represents a major site of FAHFAs synthesis [1, 2], but the biosynthetic enzymes involved are unknown [11]. Serine hydrolase carboxyl ester lipase [8] and threonine hydrolases [9] were identified as FAHFA-metabolizing enzymes. In humans, FAHFAs were detected in the serum, breast milk, meconium, and adipose tissues [1, 2, 10]. Example of PAHSA regioisomers: Network representation of FAHFA families linked according to the hydroxy-backbone and colored according to the esterified fatty acid [11] (click for full image). Our hypothesis is that novel FAHFAs derived  from omega-3 PUFA, with anti-inflammatory  properties, could be found in mice and humans and that they can beneficially affect adipose tissue metabolism in obesity,  especially low-grade  inflammation. We are also interested in FAHFA metabolic pathways, which seem to be as complex as eicosanoid-related pathways. Using experiments in cell cultures, mice and humans we explore  the structures, effects  on WAT inflammation,  WAT glucose tolerance and molecular  mechanisms of signaling  of these new lipokines. Our results present a significant advance in research of the mechanisms connecting inflammation, metabolism, and nutritional lipids. More

The role of intestine in differential metabolic effects of various lipid forms of dietary omega-3 fatty acids

Long-chain fatty acids of n-3 series (omega-3), mainly EPA and DHA of marine origin, may protect against obesity and exert hypolipidemic effects. While the mechanisms of omega-3’s effects on lipid metabolism in the liver are relatively well described, changes in metabolism in the intestine due to omega-3 are not entirely understood. 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 differential metabolic effects of omega-3 depending on the lipid form of their administration (triacylglycerols, phospholipids or wax esters), mainly with regard to the involvement of the intestine in these effects.   More

Physiological relevance of white adipose tissue plasticity and its relationship to the development of obesity

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

Effects of omega-3 in type 2 diabetic patients – new mechanisms for targeted therapy

Minor dietary components with proven biological effects play an important role in the complex treatment strategy of obesity-related diseases, however our knowledge regarding the mechanisms of their action is relatively limited. The aim of this project is to identify novel mechanisms behind the beneficial effects of omega-3 in patients with type 2 diabetes mellitus (DM), i.e. the only dietary component with clearly demonstrated beneficial effects on dyslipidemia and cardiovascular mortality and morbidity in the diabetic patients.  More

The role of endocannabinoid system in metabolic effects of marine omega-3 phospholipids

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

Achievements

Publications

Kuda, Ondřej - Březinová, Marie - Šilhavý, Jan - Landa, Vladimír - Zídek, Václav - Dodia, Ch. - Kreuchwig, F. - Vrbacký, Marek - Balas, L. - Durand, T. - Hübner, N. - Fisher, A. B. - Kopecký, Jan - Pravenec, Michal . Nrf2-Mediated Antioxidant Defense and Peroxiredoxin 6 Are Linked to Biosynthesis of Palmitic Acid Ester of 9-Hydroxystearic Acid . Diabetes 2018, roč. 67, 6, p. 1190-1199 . IF = 7.273 [ASEP] [ doi ]
Březinová, Marie - Kuda, Ondřej - Hansíková, Jana - Rombaldová, Martina - Balas, L. - Bardová, Kristina - Durand, T. - Rossmeisl, Martin - Černá, M. - Straňák, Z. - Kopecký, Jan . Levels of palmitic acid ester of hydroxystearic acid (PAHSA) are reduced in the breast milk of obese mothers . Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 2018, roč. 1863, 2, p. 126-131 . IF = 4.966 [ASEP] [ doi ]
Trnovská, J. - Šilhavý, Jan - Kuda, Ondřej - Landa, Vladimír - Zídek, Václav - Mlejnek, Petr - Šimáková, Miroslava - Strnad, Hynek - Škop, V. - Oliyarnyk, O. - Kazdová, L. - Haluzík, M. - Pravenec, Michal . Salsalate ameliorates metabolic disturbances by reducing inflammation in spontaneously hypertensive rats expressing human C-reactive protein and by activating brown adipose tissue in nontransgenic controls . PLoS ONE. 2017, roč. 12, 6, článku e0179063 . IF = 2.766 [ASEP] [ doi ]
Rombaldová, Martina - Janovská, Petra - Kopecký, Jan - Kuda, Ondřej . Omega-3 fatty acids promote fatty acid utilization and production of pro-resolving lipid mediators in alternatively activated adipose tissue macrophages . Biochemical and Biophysical Research Communications.. 2017, roč. 490, 3, p. 1080-1085 . IF = 2.559 [ASEP] [ doi ]
Pravenec, Michal - Zídek, Václav - Landa, Vladimír - Mlejnek, Petr - Šilhavý, Jan - Šimáková, Miroslava - Trnovská, J. - Škop, V. - Marková, I. - Malínská, H. - Hüttl, M. - Kazdová, L. - Bardová, Kristina - Tauchmannová, Kateřina - Vrbacký, Marek - Nůsková, Hana - Mráček, Tomáš - Kopecký, Jan - Houštěk, Josef . Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity . Physiological Research.. 2017, roč. 66, 6, p. 917-924 . IF = 1.324 [ASEP]

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Contacts

Institute of Physiology AS CR, v.v.i.
Department of Adipose Tissue Biology

Vídeňská 1083
14220 Prague 4
Czech Republic
tel. +420 241 062 554
fax. +420 241 062 599
 

Martin.Rossmeisl@fgu.cas.cz

People

MUDr. Martin Rossmeisl, Ph.D.
head of the department

MUDr. Jan Kopecký, DrSc.
deputy head of the department
RNDr. Ondřej Kuda, Ph.D.
senior researcher
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. Kateřina Adamcová
PhD student
Mgr. Jana Burešová
PhD student
Mgr. Petra Kroupová
PhD student
Mgr. Marie Březinová
PhD student
Mgr. Jiří Funda
PhD student
Mgr. Veronika Kalendová
PhD student
Mgr. Marina Oseeva
PhD student
Mgr. Gabriela Sistilli
PhD student
Ing. Lucie Leňková
PhD student
Mgr. Jana Pavlišová
PhD student (maternity leave)
Mgr. Martina Rombaldová
PhD student (maternity leave)
Bc. Ilariia Irodenko
student
Bc. Blanka Špiláková
student

Jaroslava Bémová
technician

Mgr. Karolína Seďová
technician

Jana Jahelková
technician
Ing. Adéla Krejcárková, Ph.D.
technician
Soňa Hornová
technician

Daniela Šálková
technician

 

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