Melatonin Supplementation Decreases Hypertrophic Obesity and Inflammation Induced by High-Fat Diet in Mice

Abstract

Obesity results from critical periods of positive energy balance characterized by caloric intake greater than energy expenditure. This disbalance promotes adipose tissue dysfunction which is related to other comorbidities. Melatonin is a low-cost therapeutic agent and studies indicate that its use may improve obesity-related disorders. To evaluate if the melatonin is efficient in delaying or even blocking the damages caused by excessive ingestion of a high-fat diet (HFD) in mice, as well as improving the inflammatory profile triggered by obesity herein, male C57BL/6 mice of 8 weeks were induced to obesity by a HFD and treated for 10 weeks with melatonin. The results demonstrate that melatonin supplementation attenuated serum triglyceride levels and total and LDL cholesterol and prevented body mass gain through a decreased lipogenesis rate and increased lipolytic capacity in white adipocytes, with a concomitant increment in oxygen consumption and Pgc1a and Prdm16 expression. Altogether, these effects prevented adipocyte hypertrophy caused by HFD and reflected in decreased adiposity. Finally, melatonin supplementation reduced the crown-like-structure (CLS) formation, characteristic of the inflammatory process by macrophage infiltration into white adipose tissue of obese subjects, as well as decreased the gene expression of inflammation-related factors, such as leptin and MCP1. Thus, the melatonin can be considered a potential therapeutic agent to attenuate the metabolic and inflammatory disorders triggered by obesity.

Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice

“…For metabolic activities studies (glucose uptake, TAG esterification, β-oxidation and lipolysis), adipocytes were isolated from subcutaneous ING fat depot, as previously described (26). A small number of adipocytes were photographed under an optical microscope (100× magnification) using a microscope camera (Moticam 1000; Motic, Richmond, British Columbia, Canada), and mean adipocyte diameter was determined by measuring 50 cells using Motic-Images Plus 2.0 software.…”

“…Results are expressed as nmol of palmitate incorporated into TAG per 1 × 10 6 cells h −1 . A similar procedure was used in our previous study (19,26).…”

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure

“…Melatonin improves new bone formation through mediating Wnt4 signaling and increases the uptake of oxidized vitamin C via upregulating Glut1 [35,36]. In addition, melatonin protected against obesity and relative hepatic steatosis by improving lipid dysmetabolism, stimulating brown adipose tissue (BAT) browning, inhibiting epididymal adipocyte-derived exosomal resistin and attenuating inflammation in high-fat diet (HFD)-fed mice [37][38][39][40][41]. Melatonin not only exhibited marked effects on the liver to prevent nonalcoholic steatohepatitis (NASH) and even hepatocellular carcinoma but also showed significant protection in gastrointestinal mucosa [21,42].…”

Removal of melatonin receptor type 1 signalling induces dyslipidaemia and hormonal changes in mice subjected to environmental circadian disruption

“…Melatonin supplementation was reported to improve obesity-induced resistin elevation. 35,52,53 Stubbins et al found that oestrogen protects female mice against obesity and impaired glucose tolerance, furthermore, they also report that oestrogen lowers the circulating resistin level. 43 Subsequent studies are needed to explore the mechanism of the effect of MT 1 melatonin signalling on metabolic hormones in the female melatonin-proficient mice.…”