title: Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats.
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.
authors.affiliation: Department of Pharmacology and Neurosciences Institute (CIBM), School of Medicine, University of Granada, Granada, Spain.
authors.forename: Aroa
authors.initials: A
authors.lastname: Jiménez-Aranda
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fernández-Vázquez
authors.forename: Daniel
authors.initials: D
authors.lastname: Campos
authors.forename: Mohamed
authors.initials: M
authors.lastname: Tassi
authors.forename: Lourdes
authors.initials: L
authors.lastname: Velasco-Perez
authors.forename: Dun-Xian
authors.initials: DX
authors.lastname: Tan
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Ahmad
authors.initials: A
authors.lastname: Agil
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D011924:Rats, Zucker; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D008550:Melatonin
keywords: ZDF rats; beige/brite adipose tissue; melatonin; mitochondria; nonshivering thermogenesis; obesity; white adipose tissue