Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats |
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Authors: | Aroa Jiménez‐Aranda Gumersindo Fernández‐Vázquez Daniel Campos Mohamed Tassi Lourdes Velasco‐Perez Dun‐Xian Tan Russel J Reiter Ahmad Agil |
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Institution: | 1. Department of Pharmacology and Neurosciences Institute (CIBM), School of Medicine, University of Granada, , Granada, Spain;2. Service of Endocrinology, Carlos III Hospital, , Madrid, Spain;3. Service of Microscopy, CIBM, University of Granada, , Granada, Spain;4. Department of cellular and Structural Biology, University of Texas Health Science at San Antonio, , San Antonio, TX, USA |
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Abstract: | Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown‐fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity‐related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin–eosin staining showed patches of brown‐like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2‐fold, P < 0.01) and PGC‐1α (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2‐fold the levels of PGC‐1α in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown‐fat‐like function in ZDF rats. This may contribute to melatonin′s control of body weight and its metabolic benefits. |
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Keywords: | beige/brite adipose tissue melatonin mitochondria nonshivering thermogenesis obesity white adipose tissue ZDF rats |
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