Control of adipogenic commitment by a STAT3-VSTM2A axis.
| Title: | Control of adipogenic commitment by a STAT3-VSTM2A axis. |
|---|---|
| Authors: | Al Dow M; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Silveira MAD; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.; Poliquin A; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Tribouillard L; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Fournier É; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.; Centre de recherche en données massives de l'Université Laval, Québec, Canada.; Trébaol E; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Secco B; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.; Villot R; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Tremblay F; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Bilodeau S; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.; Centre de recherche en données massives de l'Université Laval, Québec, Canada.; Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de Médecine, Université Laval, Québec, Canada.; Laplante M; Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Faculté de Médecine, Université Laval, Québec, Canada.; Centre de recherche sur le cancer de l'Université Laval, Université Laval, Québec, Canada.; Département de Médecine, Faculté de Médecine, Université Laval, Québec, Canada. |
| Source: | American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2021 Feb 01; Vol. 320 (2), pp. E259-E269. Date of Electronic Publication: 2020 Nov 16. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901226 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1555 (Electronic) Linking ISSN: 01931849 NLM ISO Abbreviation: Am J Physiol Endocrinol Metab Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Bethesda, MD. : American Physiological Society |
| MeSH Terms: | Adipocytes/*physiology ; Adipogenesis/*genetics ; Membrane Proteins/*physiology ; STAT3 Transcription Factor/*physiology; Adipose Tissue, White/metabolism ; Cell Differentiation/genetics ; Membrane Proteins/genetics ; STAT3 Transcription Factor/genetics ; Signal Transduction/genetics ; 3T3-L1 Cells ; Animals ; Gene Expression Regulation ; Male ; Mice ; Mice, Inbred C57BL |
| Abstract: | White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment are still incompletely characterized. We have recently identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a novel protein enriched in preadipocytes that amplifies adipogenic commitment. Despite the emerging role of VSTM2A in promoting adipogenesis, the molecular mechanisms regulating Vstm2a expression in preadipocytes are still unknown. To define the molecular mechanisms controlling Vstm2a expression, we have treated preadipocytes with an array of compounds capable of modulating established regulators of adipogenesis. Here, we report that Vstm2a expression is positively regulated by PI3K/mTOR and cAMP-dependent signaling pathways and repressed by the MAPK pathway and the glucocorticoid receptor. By integrating the impact of all the molecules tested, we identified signal transducer and activator of transcription 3 (STAT3) as a novel downstream transcription factor affecting Vstm2a expression. We show that activation of STAT3 increased Vstm2a expression, whereas its inhibition repressed this process. In mice, we found that STAT3 phosphorylation is elevated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression. Our findings identify STAT3 as a key transcription factor regulating Vstm2a expression in preadipocytes.NEW & NOTEWORTHY cAMP-dependent and PI3K-mTOR signaling pathways promote the expression of Vstm2a. STAT3 is a key transcription factor that controls Vstm2a expression in preadipocytes. STAT3 is activated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression. |
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| Grant Information: | 166168 Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de recherche en santé du Canada); 153318 Gouvernement du Canada | CIHR | Institute of Health Services and Policy Research (IHSPR) |
| Contributed Indexing: | Keywords: STAT3; VSTM2A; adipogenesis; adipose tissue; preadipocytes |
| Substance Nomenclature: | 0 (Membrane Proteins); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, mouse); 0 (VSTM2 protein, mouse) |
| Entry Date(s): | Date Created: 20201116 Date Completed: 20210301 Latest Revision: 20220202 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8260376 |
| DOI: | 10.1152/ajpendo.00314.2020 |
| PMID: | 33196296 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't