Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity of in rats measured by 18 F-FDG PET
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Diabetology & Metabolic Syndrome Open Access
SHORT REPORT
Melatonin deficiency decreases brown adipose tissue acute thermogenic capacity of in rats measured by 18F‑FDG PET Bruno Halpern1* , Marcio C. Mancini1, Caroline Mendes2, Camila Maria Longo Machado3, Silvana Prando3, Marcelo Tatit Sapienza3, Carlos Alberto Buchpiguel3, Fernanda Gaspar do Amaral4 and José Cipolla‑Neto2
Abstract Objective: Melatonin has been shown to increase brown adipose tissue (BAT) mass, which can lead to important metabolic effects, such as bodyweight reduction and glycemic improvement. However, BAT mass can only be meas‑ ured invasively and. The gold standard for non-invasive measurement of BAT activity is positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG PET). There is no study, to our knowledge, that has evaluated if melatonin influences BAT activity, measured by this imaging technique in animals. Methods: Three experimental groups of Wistar rats (control, pinealectomy, and pinealectomy replaced with mela‑ tonin) had an 18F-FDG PET performed at room temperature and after acute cold exposure. The ratio of increased BAT activity after cold exposure/room temperature was called “acute thermogenic capacity” (ATC) We also measured UCP-1 mRNA expression to correlate with the 18F-FDG PET results. Results: Pinealectomy led to reduced acute thermogenic capacity, compared with the other groups, as well as reduced UCP1 mRNA expression. Conclusion: Melatonin deficiency impairs BAT response when exposed to acute cold exposure. These results can lead to future studies of the influence of melatonin on BAT, in animals and humans, without needing an invasive evaluation of BAT. Keywords: Brown adipose tissue, Melatonin, Obesity, Circadian rhythms, FDG-PET, Thermogenesis, UCP-1 Background Melatonin is a pineal hormone, produced at night, which has a critical role in the synchronization of circadian rhythms, with known metabolic effects in many animal species [1, 2]. One of its metabolic effects in rodents is a reduction in body weight with a minimal decrease in food intake, suggesting an action on energy expenditure, which possibly relates to activation of brown adipose
*Correspondence: [email protected] 1 Department of Endocrinology and Metabolism, Hospital das Clinicas da Faculdade de Medicina de São Paulo, São Paulo, Brazil Full list of author information is available at the end of the article
tissue (BAT) [1–5]. Indeed, many experimental models have shown the role of melatonin on BAT recruitment [3, 6]. BAT is a thermogenic tissue, whose primary function is thermoregulation via non-shivering thermogenesis [7]. Thermogenesis occurs due to a unique and specific enzyme called uncoupling protein-1 (UCP-1), which uncouples ATP energy production in the mitochondria, generating heat [8]. Brown adipose tissue is activated by sympathetic noradrenergic stimuli, and cold is the most important physiological stimulus known [7, 8]. Recently, BAT research has increased after positron emission tomography with 2-deoxy-
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