Melatonin multiple effects on brown adipose tissue molecular machinery

Abstract

Brown adipose tissue (BAT) influences energy balance through nonshivering thermogenesis, and its metabolism daily and seasonal variations are regulated by melatonin through partially known mechanisms. We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin‐treated pinealectomized (PINX/Mel) adult rats. BAT was collected either every 3 hours over 24 hours or after cold or high‐fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold‐exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adrβ3, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1α, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub‐thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

“…All data reported above corroborate our findings suggesting that MLT plays an important role in the reduction/suppression of the atherosclerotic process; this indoleamine is able to stimulate M2 macrophages, the production of their cytokines, and preserve periaortic BAT activity, which is crucial for organism homeostasis [39].…”

“…However, it is possible that other factors that may alter 18 F-FDG distribution are not well-known [39]. In this context, our study supports the last hypothesis; in fact, we showed that 18 F-FDG uptake is very weak in the atherosclerotic mice model, but high in the same animals treated with MLT.…”

“…On the contrary, BAT is negatively correlated with the diseases reported above; it is a metabolically active fat with both local and systemic antiatherogenic effects [35][36][37]. Furthermore, it is known that BAT metabolism daily and seasonal variations are regulated by MLT through not well-known mechanisms [38,39]. Our data indicate that the aorta of the atherosclerotic mice model had more periaortic WAT with respect to the same animals treated with MLT.…”

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

“…Under optimal conditions, the circadian rhythm is reinforced in the newborn via melatonin transfer through breast milk, especially colostrum [66][67][68]. Formula-feeding can therefore contribute to the desynchronization of metabolic processes, imbalances in energy exchange, and excessive weight gain [69][70][71]. Such data has contributed towards a drive to have a nighttime formula feed that contains melatonin, which may be important for the high percentage of mothers who do not exclusively breastfeed [72], especially as this may be important to the development of the gut-brain axis [73].…”

Role of the maternal melatonin circadian rhythm absence in early catch-up growth in children

“…задержка генетического процесса становления циркадианного ритма продукции мелатонина ведет к десинхронизации метаболических процессов, нарушению энергетического обмена и избыточной прибавке массы тела [63,69,70]. Кроме того, у матерей с низкой продукцией мелатонина, как правило, снижена лактация, и большинство из них вынуждены докармливать ребенка молочными смесями, в которых уровень белка превышает его содержание в материнском молоке, что способствует еще большему скачку роста.…”