RT Journal Article
T1 Melatonin induces fat browning by transdifferentiation of white adipocytes and de novo differentiation of mesenchymal stem cells.
A1 Salagre, Diego
A1 Chayah, Meriem
A1 Molina-Carballo, Antonio
A1 Oliveras-López, María-Jesús
A1 Munoz-Hoyos, Antonio
A1 Navarro-Alarcón, Miguel
A1 Fernández-Vázquez, Gumersindo
A1 Agil, Ahmad
K1 Melatonin
K1 Obese diabetic rats
K1 Mesenchymal stem cells
K1 Adipocytes
K1 Body weight
K1 Diabesity
AB 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.
PB Royal Society of Chemistry
YR 2022
FD 2022-02-27
LK https://hdl.handle.net/10433/24876
UL https://hdl.handle.net/10433/24876
LA en
NO Food Funct., 2022,13, 3760-3775
NO Department of Pharmacology and Neurosciences Institute, School of Medicine & Biomedical Research Center, University of Granada, 18016 Granada, Spain.
NO Department of Pediatrics, School of Medicine, University of Granada (Spain). Unit of Pediatric Neurology and Neurodevelopment, Clínico San Cecilio University Hospital, the Andalusian Health Service, Granada, Spain.
NO Department of Molecular Biology and Biochemical Engineering, University Pablo de Olavide, 41013 Seville, Spain
NO Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, 18071 Granada, Spain
NO Endocrinology, Diabetes and Nutrition Center, Madrid 28006, Spain
DS RIO
RD May 9, 2026