Melatonin normalizes clinical and biochemical parameters of mild inflammation in diet‐induced metabolic syndrome in rats

Abstract

The objective of this study was to evaluate the efficacy of melatonin to affect mild inflammation in the metabolic syndrome (MS) induced by a high-fat diet in rats. Adult Wistar male rats were divided into four groups (n = 16/group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet + melatonin; and (iv) melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions for 10 wk: (a) tap water; (b) 25 μg/mL of melatonin. Plasma interleukin (IL)-1β, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and C-reactive protein (CRP) were measured at two time intervals, that is, the middle of daylight period and the middle of the scotophase. In addition, a number of somatic and metabolic components employed clinically to monitor the MS were measured. Melatonin decreased the augmented circulating levels of IL-1β, IL-6, TNF-α, IFN-γ, and CRP seen in obese rats and restored the depressed levels of IL-4 and IL-10. Rats fed with the high-fat diet showed significantly higher body weights and augmented systolic blood pressure from the third and fourth week onwards, respectively, melatonin effectively preventing these changes. In high-fat-fed rats, circulating low-density lipoprotein-cholesterol, total cholesterol, and triglyceride concentration augmented significantly, melatonin being effective to counteract these changes. Melatonin-treated rats showed a decreased insulin resistance, the highest values of plasma high-density lipoprotein-cholesterol, and the lowest values of plasma uric acid. The results indicate that melatonin is able to normalize the altered biochemical pro-inflammatory profile seen in rats fed with a high-fat diet.

Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats

“…The same was observed by us in a recent study evaluating the efficacy of melatonin to affect mild inflammation in the metabolic syndrome induced by a high-fat diet in rats [31]. Although this may imply that the main effect of melatonin on body weight is exerted peripherally through a rise in the energy expenditure, the possibility of central changes in feeding regulatory mechanisms remains open.…”

“…Although this may imply that the main effect of melatonin on body weight is exerted peripherally through a rise in the energy expenditure, the possibility of central changes in feeding regulatory mechanisms remains open. We hereby report the results of gene expression of NPY, leptin-R, POMC, prolactinreleasing peptide (PrRP), insulin-R, insulin-R substrate (IRS)-1 and IRS-2 in the medial basal hypothalamus (MBH) of the same animals employed in our previous study [31]. The changes observed were correlated with those in blood levels of leptin and adiponectin.…”

“…Water bottles were changed every other day. Because rats drank about 30 mL/day, the daily melatonin dosage used provided approximately 2.3 mg/kg melatonin [31]. Because rats drank 90%-95% of this total daily water taken up during the dark period, most melatonin was administered at the time of endogenous melatonin release.…”

“…The details about the animals and experimental design employed were given elsewhere [31]. Briefly, adult male Wistar rats were kept under standard conditions with controlled light (12:12 h light/dark schedule; lights on at 08:00 h) and temperature (22±2°C).…”

Orange beverage ameliorates high-fat-diet-induced metabolic disorder in mice

“…We observed that mice with HFD-induced MetS had high plasmatic levels of uric acid that significantly decreased with orange juice and orange beverage, but not with alcohol intake. Thus, we propose that the uric acid decrease is due to bioactive compounds found in both orange juice and orange beverage, particularly naringenin (Wang et al, 2012) and melatonin (Cano Barquilla et al, 2014). Regarding the antioxidant enzyme activities, CAT, SOD, GPx and GR levels did not present significant changes after orange juice, orange beverage or aqueous alcoholic solution intake (Table 4).…”