Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity

Abstract

A worldwide increase in the incidence of obesity indicates the unsuccessful battle against this disorder. Obesity and the associated health problems urgently require effective strategies of treatment. The new discovery that a substantial amount of functional brown adipose tissue (BAT) is retained in adult humans provides a potential target for treatment of human obesity. BAT is active metabolically and disposes of extra energy via generation of heat through uncoupling oxidative phosphorylation in mitochondria. The physiology of BAT is readily regulated by melatonin, which not only increases recruitment of brown adipocytes but also elevates their metabolic activity in mammals. It is speculated that the hypertrophic effect and functional activation of BAT induced by melatonin may likely apply to the human. Thus, melatonin, a naturally occurring substance with no reported toxicity, may serve as a novel approach for treatment of obesity. Conversely, because of the availability of artificial light sources, excessive light exposure after darkness onset in modern societies should be considered a potential contributory factor to human obesity as light at night dramatically reduces endogenous melatonin production. In the current article, the potential associations of melatonin, BAT, obesity and the medical implications are discussed.

Melatonin and ubiquitin: what’s the connection?

“…In seasonal hibernating animals melatonin is reported to be a signal related to increases in brown fat [77] and thermogenesis. this was recently shown to be the case when giving daily melatonin injections to rats led to the conversion of white fat to brown fat [78].…”

Brown adipose tissue: what have we learned since its recent identification in human adults

“…As the days start to get shorter, in anticipation of winter, BAT may slowly be recruited, in order to have sufficient levels ready for when the cold starts, and preventing body thermoneutrality from being reliant upon shivering. Melatonin is a possible player in this process, as previous studies in hibernators generally demonstrate higher BAT mass in melatonin supplemented animals (75) and, in a recent study, a higher body temperature measured by infrared thermography (which will be discussed further) was seen in mice given a melatonin rich 10 mg/kg supplement (76).…”

“…As irisin is an endogenous substance, finding other potential endogenous browning hormones or substances seems like an excellent option, as recently reviewed (87). Our group started to evaluate BAT recruitment with circadian rhythms, believing in the possible role of melatonin, as previously mentioned (75). Since hypothalamic regulation of BAT is now being clearly recognized, hypothalamic effectors, such as orexin, also appear to have therapeutic potential (17,93).…”

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

“…A past study reported that abolishing the nocturnal MLT levels by pinealectomy tends to inhibit the short-day induced body mass loss in Siberian hamsters [190]. MLT treatment consistently reduced adiposity and body mass in several rodent species [182]. Several studies have demonstrated that chronic exposure to dim light at night increases body mas gain in mice, and this effect is suggested to be mediated by the ALAN-induced MLT suppression [91,92,191,192].…”

“…blue-white LED illumination) is a highly effective inhibitor of N-acetyltransferase, the rate-limiting enzyme in MLT synthesis, thus resulting in markedly lower MLT levels and increased human health risk [180; Figure 2]. In humans, ALAN-induced suppression of MLT is suggested to be associated with obesity development intermediated by reduced metabolic activity in brown adipose tissue (BAT) [181,182]. BAT specializes in heat production, particularly in small rodents and infants, by uncoupling oxidative phosphorylation in mitochondria, mainly during cold exposure [183].…”