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.

Prophylactic Role of Oral Melatonin Administration on Neurogenesis in Adult Balb/C Mice during REM Sleep Deprivation

“…Chronic administration of melatonin is able to disrupt circadian homeostasis without affecting animals' behavior [40, 41]. However, in our study, we cannot discard that REM sleep deprivation may contribute to developing anxiety-like behaviors by disrupting circadian rhythm but, even in that case, melatonin can ameliorate these stress levels as shown by previous reports [65–67]. Therefore, previous and current evidence help support the notion that melatonin may be considered as a possible therapeutic strategy when SD occurs [68].…”

Melatonin Attenuates Aortic Endothelial Permeability and Arteriosclerosis in Streptozotocin-Induced Diabetic Rats

“…The dose of melatonin used (10 mg/kg/d) was selected based on previous studies. 36,37 Our results demonstrated that melatonin ameliorated lipid metabolism, hemodynamic and endothelial dysfunctions, and vascular hyperpermeability to a various extent in diabetic rats. Most importantly, our study is the first to show that the suppression of MLCK-and p-MYPT-mediated p-MLC expression, which was partly associated with the ERK/ p38 signal transduction pathway for the alleviation of hyperpermeability in both hyperglycemic and hypercholesterolemic states, played a crucial role in the protective effects of melatonin.…”

Melatonin reduces obesity and restores adipokine patterns and metabolism in obese ( ob/ob ) mice

“…Fresh melatonin and vehicle solutions were prepared twice a week, and the melatonin dose was adjusted to the body weight throughout the study period. Drinking bottles were covered with aluminium foil to protect melatonin from light [25].…”

“…Melatonin, a pineal indolamine secreted in a circadian pattern, has well-known antioxidant [20,21] and anti-inflammatory effects [22,23], and it is involved in energy expenditure and body fat mass regulation [24,25]. Interestingly, it was shown that the amplitude of the nocturnal pineal [26] and serum [27] melatonin peaks decreases significantly in obese animals [28].…”