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.