PMID- 24867433 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20140721 IS - 1600-079X (Electronic) IS - 0742-3098 (Linking) VI - 57 IP - 1 DP - 2014 Aug TI - Melatonin improves mitochondrial function in inguinal white adipose tissue of Zucker diabetic fatty rats. PG - 103-9 LID - 10.1111/jpi.12147 [doi] AB - 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 Zucker 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. CI - (c) 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Jimenez-Aranda, Aroa AU - Jimenez-Aranda A AD - Department of Pharmacology and Neurosciences Institute, School of Medicine, University of Granada, Granada, Spain. FAU - Fernandez-Vazquez, Gumersindo AU - Fernandez-Vazquez G FAU - Mohammad A-Serrano, Maria AU - Mohammad A-Serrano M FAU - Reiter, Russel J AU - Reiter RJ FAU - Agil, Ahmad AU - Agil A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140710 PL - England TA - J Pineal Res JT - Journal of pineal research JID - 8504412 RN - JL5DK93RCL (Melatonin) RN - SY7Q814VUP (Calcium) SB - IM MH - Adipose Tissue, White/*drug effects/*metabolism MH - Animals MH - Calcium/pharmacology MH - Cell Respiration/drug effects MH - Male MH - Melatonin/*pharmacology MH - Mitochondria/*drug effects MH - Rats MH - Rats, Zucker OTO - NOTNLM OT - Zucker diabetic fatty rats OT - beige adipose tissue OT - melatonin OT - mitochondrial function OT - white adipose tissue EDAT- 2014/05/29 06:00 MHDA- 2015/03/31 06:00 CRDT- 2014/05/29 06:00 PHST- 2014/04/08 00:00 [received] PHST- 2014/05/23 00:00 [accepted] PHST- 2014/05/29 06:00 [entrez] PHST- 2014/05/29 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - 10.1111/jpi.12147 [doi] PST - ppublish SO - J Pineal Res. 2014 Aug;57(1):103-9. doi: 10.1111/jpi.12147. Epub 2014 Jul 10.