Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet

Abstract

Backgrounds/objectives Melatonin promotes brown adipose tissue (BAT) activity, leading to body mass reduction and energy expenditure. However, the mechanisms governing these beneficial effects are not well-established. This study aimed to assess the effects of (1) melatonin on BAT and energy metabolism, and (2) fibroblast growth factor 21 (FGF21) in BAT-mediated thermogenesis. Methods Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21−/− mice consumed an HFD with or without melatonin for 8 weeks. Results Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21−/− mice. Conclusions Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.

Effects of exogenous melatonin on body mass and thermogenesis in red‐backed vole (Eothenomys miletus) between Kunming and Dali regions

“…MEL has been shown to regulate BAT (Cipolla‐Neto et al, 2014; Heldmaier & Hoffmann, 1974; Tan et al, 2011), acting as a recruiter and increasing its thermogenic capacity (Halpern et al, 2020; Heldmaier et al, 1981; Sinnamon & Pivorun, 1981; L. Xu et al, 2022). For example, MEL significantly enhanced NST by only 10 ug per animal in P. leucopus under long light conditions (Hall & Lynch, 1985).…”

“…Ability of NST in BAT depends on the UCP1 content (Buonfiglio et al, 2018; Halpern et al, 2020). MEL enhanced UCP1 content in P. sungorus (Ryu et al, 2018), Wistar rats (Halpern et al, 2020; Mendes et al, 2021), Zucker rats (Aouichat et al, 2022; Fernández Vázquez et al, 2018; Jiménez‐Aranda et al, 2013) and C57BL/6 J mice (L. Xu et al, 2022). Thermogenic activity of BAT after MEL injection in E. miletus in the present study was similar to results which were mentioned above, although there was no significant difference between the BAT mass of MEL group and SAL group in both regions, the UCP1 content was significantly increased in MEL group, which favored enhanced NST, consistent with the higher NST in E. miletus .…”

“…MEL has been shown to regulate BAT (Cipolla-Neto et al, 2014;Heldmaier & Hoffmann, 1974;Tan et al, 2011), acting as a recruiter and increasing its thermogenic capacity (Halpern et al, 2020;Heldmaier et al, 1981;Sinnamon & Pivorun, 1981;L. Xu et al, 2022).…”

Impaired Melatonin Secretion, Oxidative Stress and Metabolic Syndrome in Night Shift Work

“…In human and rat lipoaspirates, the differentiation of mesenchymal cells in contact with MT was deviated towards an increased uncoupling protein 1 (UCP1), Cbp/P300 Interacting Transactivator with Glu/Asp Rich Carboxy-Terminal Domain 1 (CITED1), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)1-α expression, which characterize beige and brown adipocytes [ 91 ]. In another experiment as well, MT upregulated the expression of thermogenic genes: Ucp1 , Prdm16 , Elovl3 , and Cidea [ 92 ]. Of note, UCP1 inhibits mitochondrial ROS production [ 93 ] probably by lowering the mitochondrial membrane potential [ 94 ].…”

“…MT has also increased the level of SOD and reduced the mitochondrial nitrate level, in Zücker diabetic fatty rats, beside an overall improvement in the mitochondrial activity related to the restoration of an efficient respiratory control [ 97 ]. Other antioxidant enzymes which were decreased by ahigh fat diet in mice ( SOD , Cat , GPX1 activity) were restored by a MT treatment [ 92 ].…”