This study aimed to evaluate changes in beige adipocytes at different times of melatonin administration, in the morning (ZT01) or in the evening (ZT11), at 30 mg/kg daily by gavage for 7 weeks or continuously with drinking water in the term of high-calorie diet-induced obesity (HCD). Melatonin received at ZT11 or with drinking water resulted in an increased area of the browning zone in the subcutaneous white adipose tissue (sWAT), even in rats with HCD (compared with Control or HCD, respectively). The beige adipocyte and lipid droplet area after melatonin use were reduced compared to those with HCD and Control, in all administration modes (group ZT01 showed smaller changes compared to ZT11 or with drinking water groups). The fibrosis level decreased and significantly differed in HCD ZT01, HCD ZT11, and HCD water compared to that in HCD; moreover, the lowest value determined in HCD water, reached the control parameters. Furthermore, the IL-1b and IL-8 level was decreased in the HCD groups under melatonin treatment at ZT11 or with drinking water compared to that in HCD. The obtained results suggest that melatonin promotes sWAT browning in rats with diet-induced obesity and influences morphological signs of normal rats depending on the time of administration. Different functional activity of beige adipocytes was observed after melatonin was used depending on the time of administration, resulting in heat production and lipolysis (the relative mass of visceral fat was likewise diminished). More rapid browning was observed when melatonin treatment was performed at 1 h before lights-off (ZT11) or continuously via drinking water. Melatonin acted on beige adipocytes of obese rats through changing some parameters such as the area of adipocytes and lipid drops, the number of lipid drops, the relative area browning of sWAT, and the level of tissue fibrosis.
KEY WORDS: Chronobiology; High-calorie diet; Fibrosis; IL-1b; Adipose tissue.