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2. Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health

Author

Lecoutre, Simon, Maqdasy, Salwan, Rizo-Roca, David, Renzi, Gianluca, Vlassakev, Ivan, Alaeddine, Lynn M., Higos, Romane, Jalkanen, Jutta, Zhong, Jiawei, Zareifi, Danae S., Frendo-Cumbo, Scott, Massier, Lucas, Hodek, Ondrej, Juvany, Marta, Moritz, Thomas, de Castro Barbosa, Thais, Omar-Hmeadi, Muhmmad, López-Yus, Marta, Merabtene, Fatiha, Abatan, Jimon Boniface, Marcelin, Geneviève, El Hachem, Elie-Julien, Rouault, Christine, Bergo, Martin O., Petrus, Paul, Zierath, Juleen R., Clément, Karine, Krook, Anna, Mejhert, Niklas, and Rydén, Mikael

Published
2024
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3. A spatiotemporal proteomic map of human adipogenesis

Author

Klingelhuber, Felix, Frendo-Cumbo, Scott, Omar-Hmeadi, Muhmmad, Massier, Lucas, Kakimoto, Pamela, Taylor, Austin J., Couchet, Morgane, Ribicic, Sara, Wabitsch, Martin, Messias, Ana C., Iuso, Arcangela, Müller, Timo D., Rydén, Mikael, Mejhert, Niklas, and Krahmer, Natalie

Published
2024
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6. Tryptophan metabolism is a physiological integrator regulating circadian rhythms

Author

Petrus, Paul, Cervantes, Marlene, Samad, Muntaha, Sato, Tomoki, Chao, Alina, Sato, Shogo, Koronowski, Kevin B, Park, Grace, Alam, Yasmine, Mejhert, Niklas, Seldin, Marcus M, Kuhn, José Manuel Monroy, Dyar, Kenneth A, Lutter, Dominik, Baldi, Pierre, Kaiser, Peter, Jang, Cholsoon, and Sassone-Corsi, Paolo

Subjects
Biochemistry and Cell Biology, Biological Sciences, Sleep Research, Nutrition, Neurosciences, 1.1 Normal biological development and functioning, Animals, Circadian Clocks, Circadian Rhythm, Liver, Mammals, Mice, Suprachiasmatic Nucleus, Tryptophan, Keywords Circadian, Metabolism, Systems biology, Circadian, Physiology, Biochemistry and cell biology
Abstract

ObjectiveThe circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids.MethodsMice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses.ResultsDietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver.ConclusionsTryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.

Published
2022

7. The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology

Author

Mejhert, Niklas, Gabriel, Katlyn R, Frendo-Cumbo, Scott, Krahmer, Natalie, Song, Jiunn, Kuruvilla, Leena, Chitraju, Chandramohan, Boland, Sebastian, Jang, Dong-Keun, von Grotthuss, Marcin, Costanzo, Maria C, Rydén, Mikael, Olzmann, James A, Flannick, Jason, Burtt, Noël P, Farese, Robert V, and Walther, Tobias C

Subjects
Biotechnology, Digestive Diseases, Nutrition, Genetics, Atherosclerosis, Human Genome, Underpinning research, 1.1 Normal biological development and functioning, Metabolic and endocrine, Affordable and Clean Energy, Animals, Cholesterol Esters, Data Mining, Databases as Topic, Genome, Humans, Inflammation, Lipid Droplets, Lipid Metabolism, Liver, Male, Mice, Inbred C57BL, Phenotype, Phosphorylation, RNA Interference, C16orf54, MSRB3, inflammation, proteasome, protein targeting, proximity labeling, sterol ester, triacylglycerol, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Lipid droplets (LDs) are organelles of cellular lipid storage with fundamental roles in energy metabolism and cell membrane homeostasis. There has been an explosion of research into the biology of LDs, in part due to their relevance in diseases of lipid storage, such as atherosclerosis, obesity, type 2 diabetes, and hepatic steatosis. Consequently, there is an increasing need for a resource that combines datasets from systematic analyses of LD biology. Here, we integrate high-confidence, systematically generated human, mouse, and fly data from studies on LDs in the framework of an online platform named the "Lipid Droplet Knowledge Portal" (https://lipiddroplet.org/). This scalable and interactive portal includes comprehensive datasets, across a variety of cell types, for LD biology, including transcriptional profiles of induced lipid storage, organellar proteomics, genome-wide screen phenotypes, and ties to human genetics. This resource is a powerful platform that can be utilized to identify determinants of lipid storage.

Published
2022

8. An integrated single cell and spatial transcriptomic map of human white adipose tissue

Author

Massier, Lucas, Jalkanen, Jutta, Elmastas, Merve, Zhong, Jiawei, Wang, Tongtong, Nono Nankam, Pamela A., Frendo-Cumbo, Scott, Bäckdahl, Jesper, Subramanian, Narmadha, Sekine, Takuya, Kerr, Alastair G., Tseng, Ben T. P., Laurencikiene, Jurga, Buggert, Marcus, Lourda, Magda, Kublickiene, Karolina, Bhalla, Nayanika, Andersson, Alma, Valsesia, Armand, Astrup, Arne, Blaak, Ellen E., Ståhl, Patrik L., Viguerie, Nathalie, Langin, Dominique, Wolfrum, Christian, Blüher, Matthias, Rydén, Mikael, and Mejhert, Niklas

Published
2023
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9. Insights from Studies of White Adipose Tissue Using Single-Cell Approaches

Author

Mejhert, Niklas, Rydén, Mikael, Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, Eckel, Juergen, editor, and Clément, Karine, editor

Published
2022
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13. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

de Rie, Derek, Abugessaisa, Imad, Alam, Tanvir, Arner, Erik, Arner, Peter, Ashoor, Haitham, Åström, Gaby, Babina, Magda, Bertin, Nicolas, Burroughs, A Maxwell, Carlisle, Ailsa J, Daub, Carsten O, Detmar, Michael, Deviatiiarov, Ruslan, Fort, Alexandre, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas J, Harshbarger, Jayson, Hasegawa, Akira, Hashimoto, Kosuke, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly J, Hon, Chung Chau, Huang, Edward, Ishizu, Yuri, Kai, Chieko, Kasukawa, Takeya, Klinken, Peter, Lassmann, Timo, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Marina, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia A, Mejhert, Niklas, Mungall, Christopher J, Noma, Shohei, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Jessica, Shin, Jay W, Swoboda, Rolf K, Tarui, Hiroshi, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter G, Wells, Christine A, Summers, Kim M, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair RR, and de Hoon, Michiel JL

Subjects
Generic health relevance, Good Health and Well Being, Animals, Cells, Cultured, Gene Expression Profiling, Gene Library, High-Throughput Nucleotide Sequencing, Humans, Mice, MicroRNAs, Molecular Sequence Annotation, Promoter Regions, Genetic, FANTOM Consortium
Abstract

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017

14. Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis

Author

Chitraju, Chandramohan, Mejhert, Niklas, Haas, Joel T, Diaz-Ramirez, L Grisell, Grueter, Carrie A, Imbriglio, Jason E, Pinto, Shirly, Koliwad, Suneil K, Walther, Tobias C, and Farese, Robert V

Subjects
Biochemistry and Cell Biology, Biological Sciences, Nutrition, Obesity, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Affordable and Clean Energy, 3T3-L1 Cells, Adipocytes, Animals, Diacylglycerol O-Acyltransferase, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Humans, Lipolysis, Mice, Triglycerides, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re-esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass but instead functions to protect the ER from lipotoxic stress and related consequences, such as adipose tissue inflammation. Our data reveal an important role for DGAT activity and TG synthesis generally in averting ER stress and lipotoxicity, with specifically DGAT1 performing this function during stimulated lipolysis in adipocytes.

Published
2017

19. Transcriptional determinants of lipid mobilization in human adipocytes

Author

Ludzki, Alison C., primary, Hansen, Mattias, additional, Zareifi, Danae, additional, Jalkanen, Jutta, additional, Huang, Zhiqiang, additional, Omar-Hmeadi, Muhmmad, additional, Renzi, Gianluca, additional, Klingelhuber, Felix, additional, Boland, Sebastian, additional, Ambaw, Yohannes A., additional, Wang, Na, additional, Damdimopoulos, Anastasios, additional, Liu, Jianping, additional, Jernberg, Tomas, additional, Petrus, Paul, additional, Arner, Peter, additional, Krahmer, Natalie, additional, Fan, Rongrong, additional, Treuter, Eckardt, additional, Gao, Hui, additional, Rydén, Mikael, additional, and Mejhert, Niklas, additional

Published
2024
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21. A Spatiotemporal Proteomic Map of Human Adipogenesis

Author

Klingelhuber, Felix, primary, Frendo-Cumbo, Scott, additional, Omar-Hmeadi, Muhmmad, additional, Taylor, Austin J., additional, Kakimoto, Pamela, additional, Couchet, Morgane, additional, Ribicic, Sara, additional, Wabitsch, Martin, additional, Messias, Ana C., additional, Iuso, Arcangela, additional, Müller, Timo D., additional, Rydén, Mikael, additional, Mejhert, Niklas, additional, and Krahmer, Natalie, additional

Published
2023
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23. Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis

Author

Rydén, Mikael, Uzunel, Mehmet, Hård, Joanna L., Borgström, Erik, Mold, Jeff E., Arner, Erik, Mejhert, Niklas, Andersson, Daniel P., Widlund, Yvonne, Hassan, Moustapha, Jones, Christina V., Spalding, Kirsty L., Svahn, Britt-Marie, Ahmadian, Afshin, Frisén, Jonas, Bernard, Samuel, Mattsson, Jonas, and Arner, Peter

Published
2015
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26. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

FANTOM Consortium, Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, J. Kenneth, Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, S. Peter, Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015

27. Leveraging Cross-Species Transcription Factor Binding Site Patterns: From Diabetes Risk Loci to Disease Mechanisms

Author

Voight, Benjamin F., Scott, Laura J., Steinthorsdottir, Valgerdur, Morris, Andrew P., Dina, Christian, Welch, Ryan P., Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S., Thorleifsson, Gudmar, McCulloch, Laura J., Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J., Raychaudhuri, Soumya, McCarroll, Steve A., Langenberg, Claudia, Hofmann, Oliver M., Dupuis, Josée, Qi, Lu, Segrè, Ayellet V., van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J., Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L., Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P., Charpentier, Guillaume, Chines, Peter S., Cornelis, Marilyn, Couper, David J., Crawford, Gabe, Doney, Alex S.F., Elliott, Katherine S., Elliott, Amanda L., Erdos, Michael R., Fox, Caroline S., Franklin, Christopher S., Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J., Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U., Johnson, Paul R.V., Jørgensen, Torben, Kao, Wen H.L., Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M., Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A., Narisu, Narisu, Nilsson, Peter, Owen, Katharine R., Payne, Felicity, Perry, John R.B., Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N. William, Robertson, Neil R., Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J., Saxena, Richa, Shields, Beverley M., Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M., Sun, Qi, Swift, Amy J., Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, van Dam, Rob M., van Haeften, Timon W., van Herpt, Thijs, van Vliet-Ostaptchouk, Jana V., Walters, G. Bragi, Weedon, Michael N., Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N., Cauchi, Stephane, Collins, Francis S., Gloyn, Anna L., Gyllensten, Ulf, Hansen, Torben, Hide, Winston A., Hitman, Graham A., Hofman, Albert, Hunter, David J., Hveem, Kristian, Laakso, Markku, Mohlke, Karen L., Morris, Andrew D., Palmer, Colin N.A., Pramstaller, Peter P., Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D., Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J., Watanabe, Richard M., Abecasis, Goncalo R., Boehm, Bernhard O., Campbell, Harry, Daly, Mark J., Hattersley, Andrew T., Hu, Frank B., Meigs, James B., Pankow, James S., Pedersen, Oluf, Wichmann, H.-Erich, Barroso, Inês, Florez, Jose C., Frayling, Timothy M., Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F., Illig, Thomas, Froguel, Philippe, van Duijn, Cornelia M., Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I., Claussnitzer, Melina, Dankel, Simon N., Klocke, Bernward, Glunk, Viktoria, Berulava, Tea, Lee, Heekyoung, Oskolkov, Nikolay, Fadista, Joao, Ehlers, Kerstin, Wahl, Simone, Hoffmann, Christoph, Qian, Kun, Rönn, Tina, Riess, Helene, Müller-Nurasyid, Martina, Bretschneider, Nancy, Schroeder, Timm, Skurk, Thomas, Horsthemke, Bernhard, Spieler, Derek, Klingenspor, Martin, Seifert, Martin, Kern, Michael J., Mejhert, Niklas, Dahlman, Ingrid, Hansson, Ola, Hauck, Stefanie M., Blüher, Matthias, Arner, Peter, Suhre, Karsten, Hsu, Yi-Hsiang, Mellgren, Gunnar, Hauner, Hans, and Laumen, Helmut

Published
2014
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28. Tryptophan metabolism is a physiological integrator regulating circadian rhythms

Author

Petrus, Paul, primary, Cervantes, Marlene, additional, Samad, Muntaha, additional, Sato, Tomoki, additional, Chao, Alina, additional, Sato, Shogo, additional, Koronowski, Kevin B., additional, Park, Grace, additional, Alam, Yasmine, additional, Mejhert, Niklas, additional, Seldin, Marcus M., additional, Monroy Kuhn, José Manuel, additional, Dyar, Kenneth A., additional, Lutter, Dominik, additional, Baldi, Pierre, additional, Kaiser, Peter, additional, Jang, Cholsoon, additional, and Sassone-Corsi, Paolo, additional

Published
2022
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32. GENE REGULATION: Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

Author

Arner, Erik, Daub, Carsten O., Vitting-Seerup, Kristoffer, Andersson, Robin, Lilje, Berit, Drabløs, Finn, Lennartsson, Andreas, Rönnerblad, Michelle, Hrydziuszko, Olga, Vitezic, Morana, Freeman, Tom C., Alhendi, Ahmad M. N., Arner, Peter, Axton, Richard, Baillie, Kenneth J., Beckhouse, Anthony, Bodega, Beatrice, Briggs, James, Brombacher, Frank, Davis, Margaret, Detmar, Michael, Ehrlund, Anna, Endoh, Mitsuhiro, Eslami, Afsaneh, Fagiolini, Michela, Fairbairn, Lynsey, Faulkner, Geoffrey J., Ferrai, Carmelo, Fisher, Malcolm E., Forrester, Lesley, Goldowitz, Daniel, Guler, Reto, Ha, Thomas, Hara, Mitsuko, Herlyn, Meenhard, Ikawa, Tomokatsu, Kai, Chieko, Kawamoto, Hiroshi, Khachigian, Levon M., Klinken, Peter S., Kojima, Soichi, Koseki, Haruhiko, Klein, Sarah, Mejhert, Niklas, Miyaguchi, Ken, Mizuno, Yosuke, Morimoto, Mitsuru, Morris, Kelly J., Mummery, Christine, Nakachi, Yutaka, Ogishima, Soichi, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry, Passier, Robert, Patrikakis, Margaret, Pombo, Ana, Qin, Xian-Yang, Roy, Sugata, Sato, Hiroki, Savvi, Suzana, Saxena, Alka, Schwegmann, Anita, Sugiyama, Daisuke, Swoboda, Rolf, Tanaka, Hiroshi, Tomoiu, Andru, Winteringham, Louise N., Wolvetang, Ernst, Yanagi-Mizuochi, Chiyo, Yoneda, Misako, Zabierowski, Susan, Zhang, Peter, Abugessaisa, Imad, Bertin, Nicolas, Diehl, Alexander D., Fukuda, Shiro, Furuno, Masaaki, Harshbarger, Jayson, Hasegawa, Akira, Hori, Fumi, Ishikawa-Kato, Sachi, Ishizu, Yuri, Itoh, Masayoshi, Kawashima, Tsugumi, Kojima, Miki, Kondo, Naoto, Lizio, Marina, Meehan, Terrence F., Mungall, Christopher J., Murata, Mitsuyoshi, Nishiyori-Sueki, Hiromi, Sahin, Serkan, Nagao-Sato, Sayaka, Severin, Jessica, de Hoon, Michiel J. L., Kawai, Jun, Kasukawa, Takeya, Lassmann, Timo, Suzuki, Harukazu, Kawaji, Hideya, Summers, Kim M., Wells, Christine, Hume, David A., Forrest, Alistair R. R., Sandelin, Albin, Carninci, Piero, and Hayashizaki, Yoshihide

Published
2015
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33. Additive effects of MicroRNAs and transcription factors on CCL2 production in human white adipose tissue

Author

Kulyte, Agne, Belarbi, Yasmina, Lorente-Cebrian, Silvia, Bambace, Clara, Arner, Erik, Daub, Carsten O., Heden, Per, Ryden, Mikael, Mejhert, Niklas, and Arner, Peter

Subjects
Analysis, Physiological aspects, Research, MicroRNA -- Research -- Analysis -- Physiological aspects, Cytokines -- Research -- Analysis, Transcription factors -- Research -- Analysis -- Physiological aspects
Abstract

White adipose tissue (WAT) function plays an important role in the development of insulin resistance/type 2 diabetes. Fat cells present in WAT secrete a number of molecules, collectively termed adipokines, [...], Adipose tissue inflammation is present in insulin-resistant conditions. We recently proposed a network of microRNAs (miRNAs) and transcription factors (TFs) regulating the production of the proinflammatory chemokine (C-C motif) ligand-2 (CCL2) in adipose tissue. We presently extended and further validated this network and investigated if the circuits controlling CCL2 can interact in human adipocytes and macrophages. The updated subnetwork predicted that miR-126/-193b/-92a control CCL2 production by several TFs, including v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) (ETS1), MYC-associated factor X (MAX), and specificity protein 12 (SP1). This was confirmed in human adipocytes by the observation that gene silencing of ETS1, MAX, or SP1 attenuated CCL2 production. Combined gene silencing of ETS1 and MAX resulted in an additive reduction in CCL2 production. Moreover, overexpression of miR-126/ -193b/-92a in different pairwise combinations reduced CCL2 secretion more efficiently than either miRNA alone. However, although effects on CCL2 secretion by co-overexpression of miR-92a/-193b and miR-92a/-126 were additive in adipocytes, the combination of miR-126/-193b was primarily additive in macrophages. Signals for miR-92a and -193b converged on the nuclear factor-κB pathway. In conclusion, TF and miRNA-mediated regulation of CCL2 production is additive and partly relayed by cell-specific networks in human adipose tissue that may be important for the development of insulin resistance/type 2 diabetes. Diabetes 2014; 63: 1248-1258 | DOI: 10.2337/db13-0702

Published
2014
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37. A promoter-level mammalian expression atlas

Author

Forrest, Alistair R. R., Kawaji, Hideya, Rehli, Michael, Kenneth Baillie, J., de Hoon, Michiel J. L., Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M., Arakawa, Takahiro, Archer, John A. C., Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan-Bhatt, Swati, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Maxwell Burroughs, A., Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S. B., Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun-ichi, Geijtenbeek, Teunis B., Gibson, Andrew P., Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Ho Sui, Shannan J., Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Huminiecki, Lukasz, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori-Katayama, Mutsumi, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Peter Klinken, S., Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F. J., Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay-sim, Alan, Manabe, Ri-ichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, de Lima Morais, David A., Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G. D., Rackham, Owen J. L., Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., ’t Hoen, Peter A. C., Tagami, Michihira, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Susan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Vladimir B., Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin, Hume, David A., Carninci, Piero, and Hayashizaki, Yoshihide

Published
2014
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38. 3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis

Author

Shen, Joanne X., primary, Couchet, Morgane, additional, Dufau, Jérémy, additional, de Castro Barbosa, Thais, additional, Ulbrich, Maximilian H., additional, Helmstädter, Martin, additional, Kemas, Aurino M., additional, Zandi Shafagh, Reza, additional, Marques, Marie‐Adeline, additional, Hansen, Jacob B., additional, Mejhert, Niklas, additional, Langin, Dominique, additional, Rydén, Mikael, additional, and Lauschke, Volker M., additional

Published
2021
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39. The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology

Author

Mejhert, Niklas, primary, Gabriel, Katlyn R., additional, Krahmer, Natalie, additional, Kuruvilla, Leena, additional, Chitraju, Chandramohan, additional, Boland, Sebastian, additional, Jang, Dong-Keun, additional, von Grotthuss, Marcin, additional, Costanzo, Maria C., additional, Flannick, Jason, additional, Burtt, Noël P., additional, Farese, Robert V., additional, and Walther, Tobias C., additional

Published
2021
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40. 3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis

Author

Shen, Joanne X., Couchet, Morgane, Dufau, Jérémy, de Castro Barbosa, Thais, Ulbrich, Maximilian H., Helmstädter, Martin, Kemas, Aurino M., Zandi Shafagh, Reza, Marques, Marie-Adeline, Hansen, Jacob B., Mejhert, Niklas, Langin, Dominique, Rydén, Mikael, Lauschke, Volker M., Shen, Joanne X., Couchet, Morgane, Dufau, Jérémy, de Castro Barbosa, Thais, Ulbrich, Maximilian H., Helmstädter, Martin, Kemas, Aurino M., Zandi Shafagh, Reza, Marques, Marie-Adeline, Hansen, Jacob B., Mejhert, Niklas, Langin, Dominique, Rydén, Mikael, and Lauschke, Volker M.

Abstract

Obesity and type 2 diabetes are strongly associated with adipose tissue dysfunction and impaired adipogenesis. Understanding the molecular underpinnings that control adipogenesis is thus of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold-free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi-omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R2 = 0.97). Integration of multi-omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis.

Published
2021

41. Spatial mapping reveals human adipocyte subpopulations with distinct sensitivities to insulin

Author

Baeckdahl, Jesper, Franzén, Lovisa, Massier, Lucas, Li, Qian, Jalkanen, Jutta, Gao, Hui, Andersson, Alma, Bhalla, Nayanika, Thorell, Anders, Ryden, Mikael, Ståhl, Patrik, Mejhert, Niklas, Baeckdahl, Jesper, Franzén, Lovisa, Massier, Lucas, Li, Qian, Jalkanen, Jutta, Gao, Hui, Andersson, Alma, Bhalla, Nayanika, Thorell, Anders, Ryden, Mikael, Ståhl, Patrik, and Mejhert, Niklas

Abstract

The contribution of cellular heterogeneity and architecture to white adipose tissue (WAT) function is poorly understood. Herein, we combined spatially resolved transcriptional profiling with single-cell RNA sequencing and image analyses to map human WAT composition and structure. This identified 18 cell classes with unique propensities to form spatially organized homo-and heterotypic clusters. Of these, three constituted mature adipocytes that were similar in size, but distinct in their spatial arrangements and transcriptional profiles. Based on marker genes, we termed these Adipo(LEP), Adipo(PLIN), and Adipo(SAA). We confirmed, in independent datasets, that their respective gene profiles associated differently with both adipocyte and whole-body insulin sensitivity. Corroborating our observations, insulin stimulation in vivo by hyperinsulinemic-euglycemic clamp showed that only Adipo(PLIN) displayed a transcriptional response to insulin. Altogether, by mining this multimodal resource we identify that human WAT is composed of three classes of mature adipocytes, only one of which is insulin responsive., QC 20211005

Published
2021
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42. In vitro and ex vivo models of adipocytes

Author

Dufau, Jérémy, primary, Shen, Joanne X., additional, Couchet, Morgane, additional, De Castro Barbosa, Thais, additional, Mejhert, Niklas, additional, Massier, Lucas, additional, Griseti, Elena, additional, Mouisel, Etienne, additional, Amri, Ez-Zoubir, additional, Lauschke, Volker M., additional, Rydén, Mikael, additional, and Langin, Dominique, additional

Published
2021
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43. Human White Adipose Tissue Displays Selective Insulin Resistance in the Obese State

Author

Mileti, Enrichetta, primary, Kwok, Kelvin HM., primary, Andersson, Daniel P., primary, Mathelier, Anthony, primary, Raman, Amitha, primary, Bäckdahl, Jesper, primary, Jalkanen, Jutta, primary, Massier, Lucas, primary, Thorell, Anders, primary, Gao, Hui, primary, Arner, Peter, primary, Mejhert, Niklas, primary, Daub, Carsten O., primary, and Rydén, Mikael, primary

Published
2021
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45. Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity

Author

Arner, Erik, Mejhert, Niklas, Kulyté, Agné, Balwierz, Piotr J., Pachkov, Mikhail, Cormont, Mireille, Lorente-Cebrián, Silvia, Ehrlund, Anna, Laurencikiene, Jurga, Hedén, Per, Dahlman-Wright, Karin, Tanti, Jean-François, Hayashizaki, Yoshihide, Rydén, Mikael, Dahlman, Ingrid, van Nimwegen, Erik, Daub, Carsten O., and Arner, Peter

Published
2012
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47. Genetic Association and Gene Expression Analysis Identify FGFR1 as a New Susceptibility Gene for Human Obesity

Author

Jiao, Hong, Arner, Peter, Dickson, Suzanne L., Vidal, Hubert, Mejhert, Niklas, Henegar, Corneliu, Taube, Magdalena, Hansson, Caroline, Hinney, Anke, Galan, Pilar, Simon, Chantal, Silveira, Angela, Benrick, Anna, Jansson, John-Olov, Bouloumié, Anne, Langin, Dominique, Laville, Martine, Debard, Cyrille, Axelsson, Tomas, Rydén, Mikael, Kere, Juha, Dahlman-Wright, Karin, Hamsten, Anders, Clement, Karine, and Dahlman, Ingrid

Published
2011

49. FIT2 is an acyl–coenzyme A diphosphatase crucial for endoplasmic reticulum homeostasis

Author

Becuwe, Michel, primary, Bond, Laura M., additional, Pinto, Antonio F.M., additional, Boland, Sebastian, additional, Mejhert, Niklas, additional, Elliott, Shane D., additional, Cicconet, Marcelo, additional, Graham, Morven M., additional, Liu, Xinran N., additional, Ilkayeva, Olga, additional, Saghatelian, Alan, additional, Walther, Tobias C., additional, and Farese, Robert V., additional

Published
2020
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