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2. Obesity causes mitochondrial fragmentation and dysfunction in white adipocytes due to RalA activation

Author

Xia, Wenmin, Veeragandham, Preethi, Cao, Yu, Xu, Yayun, Rhyne, Torrey E, Qian, Jiaxin, Hung, Chao-Wei, Zhao, Peng, Jones, Ying, Gao, Hui, Liddle, Christopher, Yu, Ruth T, Downes, Michael, Evans, Ronald M, Rydén, Mikael, Wabitsch, Martin, Wang, Zichen, Hakozaki, Hiroyuki, Schöneberg, Johannes, Reilly, Shannon M, Huang, Jianfeng, and Saltiel, Alan R

Subjects
Medical Biochemistry and Metabolomics, Medical Physiology, Biomedical and Clinical Sciences, Nutrition and Dietetics, Nutrition, Diabetes, Obesity, 2.1 Biological and endogenous factors, Stroke, Cardiovascular, Oral and gastrointestinal, Metabolic and endocrine, Animals, Humans, Male, Mice, Adipocytes, White, Adipose Tissue, Insulin Resistance, Weight Gain, ral GTP-Binding Proteins, Medical biochemistry and metabolomics, Medical physiology, Nutrition and dietetics
Abstract

Mitochondrial dysfunction is a characteristic trait of human and rodent obesity, insulin resistance and fatty liver disease. Here we show that high-fat diet (HFD) feeding causes mitochondrial fragmentation in inguinal white adipocytes from male mice, leading to reduced oxidative capacity by a process dependent on the small GTPase RalA. RalA expression and activity are increased in white adipocytes after HFD. Targeted deletion of RalA in white adipocytes prevents fragmentation of mitochondria and diminishes HFD-induced weight gain by increasing fatty acid oxidation. Mechanistically, RalA increases fission in adipocytes by reversing the inhibitory Ser637 phosphorylation of the fission protein Drp1, leading to more mitochondrial fragmentation. Adipose tissue expression of the human homolog of Drp1, DNM1L, is positively correlated with obesity and insulin resistance. Thus, chronic activation of RalA plays a key role in repressing energy expenditure in obese adipose tissue by shifting the balance of mitochondrial dynamics toward excessive fission, contributing to weight gain and metabolic dysfunction.

Published
2024

3. 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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5. 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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8. 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

9. β3-adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity

Author

Valentine, Joseph M, Ahmadian, Maryam, Keinan, Omer, Abu-Odeh, Mohammad, Zhao, Peng, Zhou, Xin, Keller, Mark P, Gao, Hui, Yu, Ruth T, Liddle, Christopher, Downes, Michael, Zhang, Jin, Lusis, Aldons J, Attie, Alan D, Evans, Ronald M, Rydén, Mikael, and Saltiel, Alan R

Subjects
Biochemistry and Cell Biology, Medical Physiology, Biomedical and Clinical Sciences, Biological Sciences, Obesity, Diabetes, Genetics, Nutrition, 2.1 Biological and endogenous factors, Cancer, Oral and gastrointestinal, 3T3-L1 Cells, Adipocytes, Animals, Catecholamines, Down-Regulation, Drug Resistance, Energy Metabolism, Lipolysis, Male, Mice, Receptors, Adrenergic, beta-3, Signal Transduction, Adipose tissue, Cell Biology, G proteins, Metabolism, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.

Published
2022

10. 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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11. Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

Author

Keinan, Omer, Valentine, Joseph M, Xiao, Haopeng, Mahata, Sushil K, Reilly, Shannon M, Abu-Odeh, Mohammad, Deluca, Julia H, Dadpey, Benyamin, Cho, Leslie, Pan, Austin, Yu, Ruth T, Dai, Yang, Liddle, Christopher, Downes, Michael, Evans, Ronald M, Lusis, Aldons J, Laakso, Markku, Chouchani, Edward T, Rydén, Mikael, and Saltiel, Alan R

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Nutrition, Diabetes, Obesity, 2.1 Biological and endogenous factors, Adaptation, Physiological, Adipocytes, Adipocytes, Beige, Animals, Cold Temperature, Energy Metabolism, Female, Glucose, Glycogen, Homeostasis, Humans, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Knockout, Thermogenesis, Uncoupling Protein 1, p38 Mitogen-Activated Protein Kinases, General Science & Technology
Abstract

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or β-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis.

Published
2021

13. 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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18. Hepatic miR-144 Drives Fumarase Activity Preventing NRF2 Activation During Obesity

Author

Azzimato, Valerio, Chen, Ping, Barreby, Emelie, Morgantini, Cecilia, Levi, Laura, Vankova, Ana, Jager, Jennifer, Sulen, André, Diotallevi, Marina, Shen, Joanne X., Miller, Anne, Ellis, Ewa, Rydén, Mikael, Näslund, Erik, Thorell, Anders, Lauschke, Volker M., Channon, Keith M., Crabtree, Mark J., Haschemi, Arvand, Craige, Siobhan M., Mori, Mattia, Spallotta, Francesco, and Aouadi, Myriam

Published
2021
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21. Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Author

Sveidahl Johansen, Olivia, Ma, Tao, Hansen, Jakob Bondo, Markussen, Lasse Kruse, Schreiber, Renate, Reverte-Salisa, Laia, Dong, Hua, Christensen, Dan Ploug, Sun, Wenfei, Gnad, Thorsten, Karavaeva, Iuliia, Nielsen, Thomas Svava, Kooijman, Sander, Cero, Cheryl, Dmytriyeva, Oksana, Shen, Yachen, Razzoli, Maria, O’Brien, Shannon L., Kuipers, Eline N., Nielsen, Carsten Haagen, Orchard, William, Willemsen, Nienke, Jespersen, Naja Zenius, Lundh, Morten, Sustarsic, Elahu Gosney, Hallgren, Cecilie Mørch, Frost, Mikkel, McGonigle, Seth, Isidor, Marie Sophie, Broholm, Christa, Pedersen, Oluf, Hansen, Jacob Bo, Grarup, Niels, Hansen, Torben, Kjær, Andreas, Granneman, James G., Babu, M. Madan, Calebiro, Davide, Nielsen, Søren, Rydén, Mikael, Soccio, Raymond, Rensen, Patrick C.N., Treebak, Jonas Thue, Schwartz, Thue Walter, Emanuelli, Brice, Bartolomucci, Alessandro, Pfeifer, Alexander, Zechner, Rudolf, Scheele, Camilla, Mandrup, Susanne, and Gerhart-Hines, Zachary

Published
2021
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23. Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Ludvik, Bernhard, Prager, Rudolf, Paulweber, Bernhard, Ebenbichler, Christoph F, Keymeulen, B, De Block, C, Grossman, Loren, Houlden, Robyn, Perron, Patrice, Ransom, Thomas, Senior, Peter, Weisnagel, S. John, Woo, Vincent, Dumas, Richard, Thompson, David, Vilsbøll, Tina, Gram, Jeppe, Juhl, Claus Bogh, Hukkanen, Janne, Lahtela, Jorma, Niskanen, Leo, O'Shea, Donal, O'Brien, Timothy, Sreenan, Seamus, Wainstein, Julio, Phillip, Moshe, Knobler, Hilla, Dotta, Francesco, Piatti, Pier Marco, Roberto, Trevisan, Gnasso, Agostino, Gulseth, Hanne, Cooper, John, Pankowska, Ewa, Lukaszewicz, Monika, Wolnik, Bogumił, Manita, Isabel, Marques, Olinda, Roque, Cristina, Príncipe, Rosa Maria, Neves, Celestino, Heitor, Susana, Ruyatkina, L, Dvoryashina, Irina, Vagapova, Gulnar, Belousova, Lidiya, Sergeeva-Kondrachenko, Marina, Peskov, Andrey, Frolova, Elena, Golovach, Albina, Kunitsyna, Marina, Krasnopeeva (Kabachkova), Natalia, Ipatko, Irina, De la Cuesta, Carmen, Tinahones, Francisco José, Rigla, Mercedes, Merino, Juan Francisco, Gómez, Luis Alberto, Fernández, Mercè, Simó, Rafael, Rydén, Mikael, Jendle, Johan, Filipsson, Karin, Eliasson, Björn, Mankovsky, Borys, Lymar, Iurii, Sokolova, Liubov, Myshanych, Galyna, Zlova, Tetiana, Vlasenko, Maryna, Kuskalo -, Petro, Courtney, Hamish, Dayan, Colin, English, Patrick, Heller, Simon, Johnson, Andrew B, Nair, Sunil, Leslie, R. D, Narendran, P, Oliver, Nick, Ramtoola, Shenaz, Shaw, Jim, Viljoen -, Adie, Al-Karadsheh, Amer, Dostou, Jean Marie, Gangi, Sumana, Gottlieb, Peter, Jerkins, Terri, Magnotti, Michael, Marks, Jennifer, Nakhle, Samer, Bonabi, Gholamreza, Myers, Lyle, Pratley, Richard, Hagopian, William, Pettus, Jeremy, von Scholten, Bernt Johan, Wesley, Johnna D, Kreiner, Frederik F, von Herrath, Matthias, Bain, Stephen C, Bode, Bruce, Clausen, Jesper Ole, Coppieters, Ken, Gaysina, Leylya, Gumprecht, Janusz, Hansen, Troels Krarup, Mathieu, Chantal, Morales, Cristobal, Mosenzon, Ofri, Segel, Stine, Tsoukas, George, and Pieber, Thomas R

Published
2021
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26. Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome.

Author

Hellberg, Anton, Salamon, Daniel, Ujvari, Dorina, Rydén, Mikael, and Hirschberg, Angelica Lindén

Subjects
WEIGHT loss, BODY mass index, WAIST-hip ratio, WEIGHT gain, OBESITY in women, ADIPOSE tissues
Abstract

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18–40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (−2.2%, p = 0.0014), while there was no significant weight loss in the control group (−1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = −0.41, p = 0.002; R = −0.31, p = 0.023 and R = −0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Decreased mitochondrial creatine kinase 2 impairs skeletal muscle mitochondrial function independently of insulin in type 2 diabetes.

Author

Rizo-Roca, David, Guimarães, Dimitrius Santiago P. S. F., Pendergrast, Logan A., Di Leo, Nicolas, Chibalin, Alexander V., Maqdasy, Salwan, Rydén, Mikael, Näslund, Erik, Zierath, Juleen R., and Krook, Anna

Subjects
TYPE 2 diabetes, CREATINE kinase, OXIDATION of glucose, INSULIN resistance, HIGH-fat diet
Abstract

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet–fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes. Editor's summary: Increased plasma creatine is associated with type 2 diabetes, but causation has not been established. Rizo-Roca et al. show that men with type 2 diabetes had increased plasma creatine and decreased muscle phosphocreatine, which was associated with poor glucose handling. In myotubes in vitro, silencing the mitochondria-associated sarcomeric mitochondrial creatine kinase 2 (Ckmt2) gene resulted in impaired mitochondrial functions. In mice fed a high-fat diet, creatine supplementation had no effect on glucose handling, but overexpression of Ckmt2 in muscle improved mitochondrial functions. Data from humans and mice showed that exercise increased CKMT2 and metrics of mitochondrial functions. These results suggest that creatine changes are a consequence rather than a cause of insulin resistance in type 2 diabetes. —Brandon Berry [ABSTRACT FROM AUTHOR]

Published
2024
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29. IMPROVE 2022 International Meeting on Pathway‐Related Obesity: Vision of Excellence

Author

Kühnen, Peter, primary, Argente, Jesús, additional, Clément, Karine, additional, Dollfus, Hélène, additional, Dubern, Béatrice, additional, Farooqi, Sadaf, additional, de Groot, Corjan, additional, Grüters, Annette, additional, Holm, Jens‐Christian, additional, Hopkins, Mark, additional, Kleinendorst, Lotte, additional, Körner, Antje, additional, Meeker, David, additional, Rydén, Mikael, additional, von Schnurbein, Julia, additional, Tschöp, Matthias, additional, Yeo, Giles S. H., additional, Zorn, Stefanie, additional, and Wabitsch, Martin, additional

Published
2024
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30. P2Y13 receptor deficiency favors adipose tissue lipolysis and worsens insulin resistance and fatty liver disease

Author

Duparc, Thibaut, primary, Gore, Emilia, additional, Combes, Guillaume, additional, Beuzelin, Diane, additional, Pires Da Silva, Julie, additional, Bouguetoch, Vanessa, additional, Marquès, Marie-Adeline, additional, Velazquez, Ana, additional, Viguerie, Nathalie, additional, Tavernier, Geneviève, additional, Arner, Peter, additional, Rydén, Mikael, additional, Langin, Dominique, additional, Sioufi, Nabil, additional, Nasser, Mohamad, additional, Cabou, Cendrine, additional, Najib, Souad, additional, and Martinez, Laurent O., additional

Published
2024
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32. Glutamine Links Obesity to Inflammation in Human White Adipose Tissue

Author

Petrus, Paul, Lecoutre, Simon, Dollet, Lucile, Wiel, Clotilde, Sulen, André, Gao, Hui, Tavira, Beatriz, Laurencikiene, Jurga, Rooyackers, Olav, Checa, Antonio, Douagi, Iyadh, Wheelock, Craig E., Arner, Peter, McCarthy, Mark, Bergo, Martin O., Edgar, Laurienne, Choudhury, Robin P., Aouadi, Myriam, Krook, Anna, and Rydén, Mikael

Published
2020
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33. IMPROVE 2022 International Meeting on Pathway-Related Obesity:Vision of Excellence

Author

Kühnen, Peter, Argente, Jesús, Clément, Karine, Dollfus, Hélène, Dubern, Béatrice, Farooqi, Sadaf, de Groot, Corjan, Grüters, Annette, Holm, Jens Christian, Hopkins, Mark, Kleinendorst, Lotte, Körner, Antje, Meeker, David, Rydén, Mikael, von Schnurbein, Julia, Tschöp, Matthias, Yeo, Giles S.H., Zorn, Stefanie, Wabitsch, Martin, Kühnen, Peter, Argente, Jesús, Clément, Karine, Dollfus, Hélène, Dubern, Béatrice, Farooqi, Sadaf, de Groot, Corjan, Grüters, Annette, Holm, Jens Christian, Hopkins, Mark, Kleinendorst, Lotte, Körner, Antje, Meeker, David, Rydén, Mikael, von Schnurbein, Julia, Tschöp, Matthias, Yeo, Giles S.H., Zorn, Stefanie, and Wabitsch, Martin

Abstract

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany.

Published
2024

34. Exercise-induced crosstalk between immune cells and adipocytes in humans:Role of oncostatin-M

Author

Dollet, Lucile, Lundell, Leonidas S., Chibalin, Alexander V., Pendergrast, Logan A., Pillon, Nicolas J., Lansbury, Elizabeth L., Elmastas, Merve, Frendo-Cumbo, Scott, Jalkanen, Jutta, de Castro Barbosa, Thais, Cervone, Daniel T., Caidahl, Kenneth, Dmytriyeva, Oksana, Deshmukh, Atul S., Barrès, Romain, Rydén, Mikael, Wallberg-Henriksson, Harriet, Zierath, Juleen R., Krook, Anna, Dollet, Lucile, Lundell, Leonidas S., Chibalin, Alexander V., Pendergrast, Logan A., Pillon, Nicolas J., Lansbury, Elizabeth L., Elmastas, Merve, Frendo-Cumbo, Scott, Jalkanen, Jutta, de Castro Barbosa, Thais, Cervone, Daniel T., Caidahl, Kenneth, Dmytriyeva, Oksana, Deshmukh, Atul S., Barrès, Romain, Rydén, Mikael, Wallberg-Henriksson, Harriet, Zierath, Juleen R., and Krook, Anna

Abstract

The discovery of exercise-regulated circulatory factors has fueled interest in organ crosstalk, especially between skeletal muscle and adipose tissue, and the role in mediating beneficial effects of exercise. We studied the adipose tissue transcriptome in men and women with normal glucose tolerance or type 2 diabetes following an acute exercise bout, revealing substantial exercise- and time-dependent changes, with sustained increase in inflammatory genes in type 2 diabetes. We identify oncostatin-M as one of the most upregulated adipose-tissue-secreted factors post-exercise. In cultured human adipocytes, oncostatin-M enhances MAPK signaling and regulates lipolysis. Oncostatin-M expression arises predominantly from adipose tissue immune cell fractions, while the corresponding receptors are expressed in adipocytes. Oncostatin-M expression increases in cultured human Thp1 macrophages following exercise-like stimuli. Our results suggest that immune cells, via secreted factors such as oncostatin-M, mediate a crosstalk between skeletal muscle and adipose tissue during exercise to regulate adipocyte metabolism and adaptation.

Published
2024

38. The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

Author

Jensen, Charlotte Harken, Kosmina, Rok, Rydén, Mikael, Baun, Christina, Hvidsten, Svend, Andersen, Marianne Skovsager, Christensen, Louise Lehmann, Gastaldelli, Amalia, Marraccini, Paolo, Arner, Peter, Jørgensen, Christian Damsgaard, Laborda, Jorge, Holst, Jens Juul, and Andersen, Ditte Caroline

Published
2019
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39. Specific loss of adipocyte CD248 improves metabolic health via reduced white adipose tissue hypoxia, fibrosis and inflammation

Author

Petrus, Paul, Fernandez, Tara L., Kwon, Michelle M., Huang, Jenny L., Lei, Victor, Safikhan, Nooshin Seyed, Karunakaran, Subashini, O'Shannessy, Daniel J., Zheng, Xiaowei, Catrina, Sergiu-Bogdan, Albone, Earl, Laine, Jukka, Virtanen, Kirsi, Clee, Susanne M., Kieffer, Timothy J., Noll, Christophe, Carpentier, André C., Johnson, James D., Rydén, Mikael, and Conway, Edward M.

Published
2019
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41. Targeted Proteomics Reveals Functional Targets for Early Diabetes Susceptibility in Young Adults

Author

Shah, Ravi V., primary, Zhong, Jiawei, additional, Massier, Lucas, additional, Tanriverdi, Kahraman, additional, Hwang, Shih-Jen, additional, Haessler, Jeffrey, additional, Nayor, Matthew, additional, Zhao, Shilin, additional, Perry, Andrew S., additional, Wilkins, John T., additional, Shadyab, Aladdin H., additional, Manson, JoAnn E., additional, Martin, Lisa, additional, Levy, Daniel, additional, Kooperberg, Charles, additional, Freedman, Jane E., additional, Rydén, Mikael, additional, and Murthy, Venkatesh L., additional

Published
2024
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42. 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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43. Diagnostic challenges in patients with reninomas and extrarenal renin‐producing tumours.

Author

Fabian, Botond, Ragnarsson, Oskar, Prazic, Aleksandar, Rydén, Mikael, Volpe, Cristina, and Lindgren, Ola

Subjects
MAGNETIC resonance imaging, RENAL veins, HYPOKALEMIA, TUMORS
Abstract

Renin‐secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work‐up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin‐producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work‐up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose‐positron emission tomography‐CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Exercise-induced crosstalk between immune cells and adipocytes in humans: Role of oncostatin-M

Author

Dollet, Lucile, primary, Lundell, Leonidas S., additional, Chibalin, Alexander V., additional, Pendergrast, Logan A., additional, Pillon, Nicolas J., additional, Lansbury, Elizabeth L., additional, Elmastas, Merve, additional, Frendo-Cumbo, Scott, additional, Jalkanen, Jutta, additional, de Castro Barbosa, Thais, additional, Cervone, Daniel T., additional, Caidahl, Kenneth, additional, Dmytriyeva, Oksana, additional, Deshmukh, Atul S., additional, Barrès, Romain, additional, Rydén, Mikael, additional, Wallberg-Henriksson, Harriet, additional, Zierath, Juleen R., additional, and Krook, Anna, additional

Published
2023
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50. Liver macrophages regulate systemic metabolism through non-inflammatory factors

Author

Morgantini, Cecilia, Jager, Jennifer, Li, Xidan, Levi, Laura, Azzimato, Valerio, Sulen, André, Barreby, Emelie, Xu, Connie, Tencerova, Michaela, Näslund, Erik, Kumar, Chanchal, Verdeguer, Francisco, Straniero, Sara, Hultenby, Kjell, Björkström, Niklas K., Ellis, Ewa, Rydén, Mikael, Kutter, Claudia, Hurrell, Tracey, Lauschke, Volker M., Boucher, Jeremie, Tomčala, Aleš, Krejčová, Gabriela, Bajgar, Adam, and Aouadi, Myriam

Published
2019
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