Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats

Abstract

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown-fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity-related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin-eosin staining showed patches of brown-like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2-fold, P < 0.01) and PGC-1α (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2-fold the levels of PGC-1α in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown-fat-like function in ZDF rats. This may contribute to melatonin's control of body weight and its metabolic benefits.

A Double-Blind, Placebo-Controlled Trial Related to the Effects of Melatonin on Oxidative Stress and Inflammatory Parameters of Obese Women

“…During the past decade, several studies have supported the potential health benefits of melatonin including antioxidation, anti-inflammatory, immunomodulatory, body fat mass, and weight regulatory effects [10][11][12][13][24][25][26][27][28].…”

“…Nowadays, obesity management and its adverse health consequences require application of new generation of dietary supplements in addition to healthy lifestyles, which might help weight loss and ameliorate some detrimental effects of obesity [8,9]. Melatonin is one of the nutritional supplements, which has been taken into consideration for weight control lately [10][11][12]. Obesity induced lipo and glucotoxicity increases reactive oxygen species (ROS) production that triggers the proinflammatory cascade and potentiates tissue damage.…”

“…It seems more reasonable to consider the other means in addition to the current treatments for obesity such as dietary intervention, behavioral modification, and lifestyle changes, to prevent the adverse health consequences of obesity and related metabolic disorders [8,9]. New data have revealed the beneficial effects of melatonin as a nutritional supplement in weight regulation [10,11]. Melatonin (N-acetyl-5-methoxytryptamine) in mammals is synthesized in several cells, tissues, and organs mainly for local utilization (autocrine and paracrine actions) and the circulating melatonin is mostly provided by the pineal gland [11,12].…”

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).…”

Potential benefits of melatonin in organ transplantation: a review

“…Numerous studies have provided data showing that melatonin protects against the IRI-induced impairment of mitochondrial respiration, ATP synthesis, mitochondrial swelling, and LPO (Okatani et al 2003, Kireev et al 2013. Melatonin also reduces electron leakage from the respiratory chain that limits free radical generation and increases the expression of uncoupling protein, which is thought to improve electron flow through the respiratory chain and prevent mitochondrial O 2 ·− generation by increasing proton flow into the matrix (Pappolla et al 1999, Jiménez-Aranda et al 2013.…”