SMYD3 : a new regulator of adipocyte precursor proliferation at the early steps of differentiation

Article Article scientifique Article SMYD3 : a new regulator of adipocyte precursor proliferation at the early steps of differentiation eng 2023-12-26 2024-04 author Sajic Tatjana Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.,Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. 647061 author Ferreira Gomes Chayenne Karine Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. author Gasser Marie Charlotte 0000-0002-7242-1141 Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.,Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. 833480 author Caputo Tiziana 0000-0002-3854-5677 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. author Bararpour Nasim 0000-0001-6244-8781 Stanford Center for Genomics and Personalized Medicine, Stanford, CA, USA.,Department of Genetics, Stanford University, Stanford, CA, USA. author Landaluce-Iturriria Esther Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. author Augsburger Marc 0000-0002-5606-3831 Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland. 677425 author Walter Nadia Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 134481 Services communs de la faculté de médecine (SCMU) author Hainard Alexandre 0009-0006-7403-3261 Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 635700 Services communs de la faculté de médecine (SCMU) author Lopez-Mejia Isabel C 0000-0001-5918-0227 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. author Fracasso Tony Unit of Forensic Medicine, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland. 731584 Institut de médecine légale (COLEG) author Thomas Aurélien Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.,Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. 647674 author Gilardi Federica 0000-0001-5421-2779 Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland. federica.gilardi@chuv.ch.,Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland. federica.gilardi@chuv.ch. 891679 557-566 10.1038/s41366-023-01450-x 38148333 0307-0565 PMC10978492 https://www.nature.com/articles/s41366-023-01450-x Background: In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to a hypertrophic growth that is accompanied by the development of inflammation and metabolic dysfunction. However, the molecular mechanisms underlying the fine-tuned regulation of adipose tissue expansion are far from being understood. Methods: We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low inflammation (Low-INFL), showed reduced adipose tissue inflammation, as opposed to those developing the expected inflammatory response (Hi-INFL). We identified the discriminants between Low-INFL and Hi-INFL vWAT samples and explored their function in Adipose-Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. Results: vWAT proteomics allowed us to quantify 6051 proteins. Among the candidates that most differentiate Low-INFL from Hi-INFL vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in Low-INFL, as compared to Hi-INFL. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was so far unknown, was another top-scored hit. SMYD3 expression was significantly higher in Low-INFL vWAT, as confirmed by western blot analysis. Using AD-hMSCs in culture, we found that SMYD3 mRNA and protein levels decrease rapidly during the adipocyte differentiation. Moreover, SMYD3 knock-down before adipocyte differentiation resulted in reduced H3K4me3 and decreased cell proliferation, thus limiting the number of cells available for adipogenesis. Conclusions: Our study describes an important role of SMYD3 as a newly discovered regulator of adipocyte precursor proliferation during the early steps of adipogenesis. Adipocytes / metabolism Adipogenesis / physiology Adipose Tissue, White / metabolism Animals Cell Differentiation / genetics Cell Proliferation Histone-Lysine N-Methyltransferase / metabolism Humans Hypertrophy / metabolism Inflammation / metabolism Mice Mice, Inbred C57BL Obesity Dewey 614.1 Swiss National Science Foundation Linking obesity, metabolic disorders, and inflammation via metabolomics and epigenetics 156771 CH Swiss National Science Foundation Impact of metallothionein polymorphism on the toxic effect of trace elements on human adipose tissue 182420 CH Swiss National Science Foundation Macronutrition and signal-induced regulation of RNA splicing in adipose tissue depots 193166 CH 67 Institut de médecine légale 22A2 false 953 Groupe Fracasso Tony 959 International journal of obesity 48 4 ef4bb529-b5a4-4e19-a1c8-e847186761d5 Article (Published version) Public Article_scientifique_from_crossref.pdf 2899408 application/pdf CC BY-4.0 ea52da46283c271163ceb20c59084769fa109f80eca35c11f0d25077ecdf1af3 58e504c2-5e0e-4c0e-975f-b8c6878eacfb Supplemental data Public 41366_2023_1450_MOESM1_ESM.pdf 612486 application/pdf 36991eb52f6410a7770087d60f32294c366820e1b2cb85df87a7fabebadbe632 7aa338e0-0b90-470f-93e9-4d6c7ff41883 Supplemental data Public 41366_2023_1450_MOESM2_ESM.xlsx 1106274 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet f90b8523bfa5c145228295ea317e7ba78c1f9d4e2bc7cbe1caeef8dd24feeaa8 272a4f60-9841-4f6f-a4f2-ea626af5a5b6 Supplemental data Public 41366_2023_1450_MOESM3_ESM.xlsx 29950 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 67dce57a8f991ad2a229a8559f6ba06b20371e09e5d926cb50a467c9ee35ca47 38672c47-3ef1-45db-9fd5-a303e2305b79 Supplemental data Public 41366_2023_1450_MOESM4_ESM.xlsx 29357 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet aea28512784268b5f9e859dfd20511c20c334f3c8710cf2e356faee3598b9f2f openAccess Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de médecine légale

Title	Published in	Year	Views	Downloads

SMYD3 : a new regulator of adipocyte precursor proliferation at the early steps of differentiation	International journal of obesity	2024	8	76
Impact of the toxic effects of heavy metals on human adipose tissue		2023	497	561

Archive ouverte UNIGE

Gasser, Marie Charlotte

account_balance Affiliation entities

Affiliation entities