Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells
| Autor: | Diego Salagre, Meriem Chayah, Antonio Molina-Carballo, María-Jesús Oliveras-López, Antonio Munoz-Hoyos, Miguel Navarro-Alarcón, Gumersindo Fernández-Vázquez, Ahmad Agil |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Digibug. Repositorio Institucional de la Universidad de Granada instname |
| ISSN: | 2042-650X 2042-6496 |
| DOI: | 10.1039/d1fo04360a |
| Popis: | This research was partially supported by grant SAF2016-79794R from the Ministerio de Ciencia e Innovacion (Spain), European Regional Development Fund (ERDF), University of Granada and FEDER Funds grant number B-CTS-102-UGR20. The authors thank Antonio Tirado for their technical assistance. The role of melatonin in obesity control is extensively accepted, but its mechanism of action is still unclear. Previously we demonstrated that chronic oral melatonin acts as a brown-fat inducer, driving subcutaneous white adipose tissue (sWAT) into a brown-fat-like function (beige) in obese diabetic rats. However, immunofluorescence characterization of beige depots in sWAT and whether melatonin is a beige-fat inducer by de novo differentiation and/or transdifferentiation of white adipocytes are still undefined. Lean (ZL) and diabetic fatty (ZDF) Zücker rats were subdivided into two groups, control (C) and oral melatonin-supplemented (M, 10 mg kg−1 day−1) for 6 weeks. Mesenchymal stem cells (MSCs) were isolated from both rat inguinal fat and human lipoaspirates followed by adipogenesis assays with or without melatonin (50 nM for 12 h in a 24 h period, 12 h+/12 h−) mimicking the light/dark cycle. Immunofluorescence and western-blot assays showed the partial transdifferentiation of white adipocytes in both ZL and ZDF rats, with increasing thermogenic and beige markers, UCP1 and CITED1 and decreasing white adipocyte marker ASC-1 expression. In addition, melatonin increased UCP1, CITED1, and PGC1- α expression in differentiated adipocytes in both rats and humans. These results demonstrate that melatonin increases brown fat in obese diabetic rats by both adipocyte transdifferentiation and de novo differentiation. Furthermore, it promotes beige MSC adipogenesis in humans. This may contribute to the control of body weight attributed to melatonin and its metabolic benefits in human diabesity. Spanish Government SAF2016-79794R European Commission B-CTS-102-UGR20 University of Granada |
| Databáze: | OpenAIRE |
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