title: Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats.
abstract: Mitochondrial dysfunction in adipose tissue may contribute to obesity-related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity-related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats mainly through a reduction of proton leaking component of respiration (state 4) (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05) and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled respiration. Melatonin also lowered mitochondrial oxidative status by reducing nitrite levels and by increasing superoxide dismutase activity. Moreover, melatonin treatment also caused a profound inhibition of Ca-induced opening of mPTP in isolated mitochondria from both types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity-related metabolic disorders such as diabetes and dyslipidemia of ZDF rats.
authors.affiliation: Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, Granada, Spain.
authors.forename: Aroa
authors.initials: A
authors.lastname: Jimenéz-Aranda
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fernández-Vázquez
authors.forename: María
authors.initials: M
authors.lastname: Mohammad A-Serrano
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Ahmad
authors.initials: A
authors.lastname: Agil
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D008550:Melatonin; D002118:Calcium
keywords: Zücker diabetic fatty rats; beige adipose tissue; melatonin; mitochondrial function; white adipose tissue