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Regulation of Lipogenesis in Human Adipose Tissue : Effect of Metabolic Stress, Dietary Intervention and Aging Veronika Sramkova

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Regulation of Lipogenesis in Human Adipose Tissue : Effect of Metabolic Stress, Dietary Intervention and Aging Veronika Sramkova Regulation of lipogenesis in human adipose tissue : effect of metabolic stress, dietary intervention and aging Veronika Sramkova To cite this version: Veronika Sramkova. Regulation of lipogenesis in human adipose tissue : effect of metabolic stress, dietary intervention and aging. Human genetics. Université Paul Sabatier - Toulouse III, 2017. English. NNT : 2017TOU30234. tel-01920913 HAL Id: tel-01920913 https://tel.archives-ouvertes.fr/tel-01920913 Submitted on 13 Nov 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Declaration Hereby I declare that this doctoral thesis is based on experiments performed during my Ph.D. studies at the Department for the Study of Obesity and Diabetes, at Third Faculty of Medicine, Charles University, in Prague and in Obesity Research Laboratory, INSERM, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC - UMR1048), in Toulouse. Also, I declare that this thesis was written by me, that I cited properly all mentioned sources and literature and that this work was not used to obtain any other or same degree. This thesis was supported by GAP301/11/0748 of the Grant Agency of the Czech Republic, IGA NT 14486 of the Internal Grant Agency of the Ministry of Health of the Czech Republic, AZV 16-29182A of Ministry of Health/Grant Agency for Health Research of the Czech Republic, PRVOUK, Obelip from Agence Nationale de la Recherche, sponsorship from Region of Midi-Pyrénées, scholarship from Czech Ministry of Education, Youth and Sports in Czech Republic and scholarship for cotutelle from French government. I thank sincerely all the parties for their support. I agree with permanent deposition of electronic version of my work in the database of inter-university project Theses.cz in order to constantly control similarities of qualification thesis. In Prague, 6.7.2017 Veronika Šrámková Signature: 2 Identification record ŠRÁMKOVÁ, Veronika. Regulace lipogeneze v lidské tukové tkáni: Efekt metabolického stresu, kalorické restrikce a stárnutí. [Regulation of lipogenesis in human adipose tissue: Effect of metabolic stress, dietary intervention and aging]. Praha, 2017. 160 stran, 2 přílohy. Dizertační práce. Univerzita Karlova, Praha, 3. lékařská fakulta, Oddělení pro studium obesity a diabetu. 3. LF UK. Vedoucí závěrečné práce Mgr. Lenka Rossmeislová, Ph.D. a Prof. Dominique Langin, D.V.M., Ph.D.. Klíčová slova: tuková tkáň, lipogeneze, adipogeneze, endoplazmatické retikulum, kalorická restrikce, stárnutí Key words: adipose tissue, lipogenesis, adipogenesis, endoplasmic reticulum, calorie restriction, aging. 3 Acknowledgement This thesis was performed as a cotutelle under the supervision of Lenka Rossmeislová and Dominique Langin, in the franco-czech laboratories of Department for the study of Obesity and Diabetes (earlier Department of Sports Medicine), Third Faculty of Medicine, Charles University, Prague, Czech Republic and at the Institute of Cardiovascular and Metabolic Diseases (I2MC), INSERM, U1048, Toulouse, France. There are no words to express my immense thanks and gratitude to my supervisor Lenka Rossmeislová. Thank you for your professional guidance, advices, quick responses, positive attitude and psychological support. And all of that not only in Prague, but also in Toulouse! During troubled times when I did not see the things in pink and nearly lost confidence in my work, you still believed in me and had no doubts. All that made me somehow to continue. Your kindness, straightness and fair-minded actions during the leadership of the lab were very inspiring and motivating! My heartfelt thanks belong to my second supervisor Dominique Langin. Thank you for giving me this opportunity (without even knowing me!) to work on very interesting projects in the laboratory in Toulouse which has such a stimulating environment. Thank you for understanding, time, help, rapid and apt responses. Your knowledge in the field of obesity and tiredness enthusiasm is more than only appreciated. Last, but not least, thank you for having shown me the right internet site, where I came across a good bicycle to drive me every day into the lab! Special thank belongs to Vladimír Štich for giving me the occasion to join his research group and for his though-provoking scientific remarks during the lab meetings. Next, I would like to thank all the members from the Department for the Study of Obesity and Diabetes for their help, cooperation and friendly attitude during the time of everyday hard-work. Particularly, to Jana Kračmerová for her endless sense of humour, to Eva Krauzová for her interest and concern about good health of all members of the laboratory, to Lenka Beranová for her amusing stories which made the hours in cell culture room much faster, to Barbora Svobodová for her skilful assistance with FACS and of course for our pizza Thursdays (!), to Iveta Humlová for her everyday willingness to help, to Marek Štěpán for positive attitude, to Michal Koc for his training in the field of ERS biology and to Míša Šiklová for her peaceful aura which diffuses around always at the right time. 4 Big thanks belong also to people on the French side of the lab Tremendous thanks and respect to Aline Mairal, for your generosity, laboratory ease and skills, support, optimistic mind, ability to be at the right place when people need you the most, ability to transfer the „know-how“, ability to listen and empathize and for your specific sense of humour. Thank you Aline for all of that! I would like to thank also to Marie-Adeline Marques for her skilful assistance with cell culture. Big thanks to Corinne Lefort for her lessons of French language during the „four o´clock coffees“, help with French translations and her super-detailed protocols. Thanks to Geneviève Tavernier for your help with professional French translation. Enormous thank to Sophie Bonnel for your friendship and help, especially after our visit of „Warrior Adventure“. You were like my sister and I will never forget it! I would like to thank to the „girls“: Marianne Houssier, Pauline Morigny, Claire Laurens, Diane Beuzelin, Marine Coué and Claire Ghilain to take me among them. Thanks for a friendship to girls from the „next door“: Gwendoline Astre, Nancy Geoffre and Ophélie Pereira. My sincere thank and deep gratitude belongs to Nathalie Viguerie for her kindness, care, inspiration, open mind and very interesting discussions from which I learnt a lot! Thank you for taking me into that great ApoM project! Also, I would like to express my gratitude for the possibility to go on BioHC Summer School into Archamps, it was a great experience. Finally, thanks for borrowing me the crushes, because without them, I would not be able to come home last time. I would like to thank to my dear parents to always supporting me. Thanks also to my sister Baruška, brother Filip and friends (Kristy and Pavel) for your support and funny comments! I thank to my formidable husband Martin. Thanks for your endless care, understanding, listening, support, courage, patience and love. 5 Contents Declaration ................................................................................................................................ 2 Identification record ................................................................................................................ 3 List of abbreviations................................................................................................................. 9 Summary ................................................................................................................................. 12 Résumé .................................................................................................................................... 14 Shrnutí ..................................................................................................................................... 16 1 Introduction into biology of adipose tissue ................................................................... 18 1.1. Adipose tissue ............................................................................................................ 19 1.1.1 White adipose tissue ........................................................................................... 19 1.1.2 Brown and brite adipose tissue........................................................................... 20 1.1.3 Cellular composition of white adipose tissue ..................................................... 21 1.1.3.1 Adipocytes ...................................................................................................... 21 1.1.3.2 Stromal vascular fraction ................................................................................ 21 1.1.3.2.1 Adipose tissue stem cells .......................................................................... 21 1.1.3.2.2 Immune cells ............................................................................................. 23 1.1.4 Extracellular matrix ............................................................................................ 24
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