Melatonin absence leads to long-term leptin resistance and overweight in rats

Daniella Buonfiglio, Rafaela Parthimos, Rosana Dantas, Raysa Cerqueira Silva, Guilherme Gomes, Jéssica Andrade-Silva, Angela Ramos-Lobo, Fernanda Gaspar Amaral, Raphael Matos, José Sinésio, Lívia Clemente Motta-Teixeira, José Donato, Russel J Reiter, José Cipolla-Neto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Melatonin (Mel), a molecule that conveys photoperiodic information to the organisms, is also involved in the regulation of energy homeostasis. Mechanisms of action of Mel in the energy balance remain unclear; herein we investigated how Mel regulates energy intake and expenditure to promote a proper energy balance. Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX) and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the drinking water exclusively during the dark phase for 13 weeks. After this treatment period, rats were subjected to a 24-h fasting test, an acute leptin responsiveness test and cold challenge. Mel treatment reduced food intake, body weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats exhibited leptin resistance; this was likely related to the capacity of leptin to affect body weight, food intake, and hypothalamic signal-transducer and activator of transcription 3 phosphorylation, all of which were reduced. Mel treatment restored leptin sensitivity in PINX rats. An increased hypothalamic expression of agouti-related peptide (Agrp), neuropeptide Y, and Orexin was observed in the PINX group while Mel treatment reduced the expression of Agrp and Orexin. In addition, PINX rats presented lower UCP1 protein levels in the brown adipose tissue and required higher tail vasoconstriction to get a proper thermogenic response to cold challenge. Our findings reveal a previously unrecognized interaction of Mel and leptin in the hypothalamus to regulate the energy balance. These findings may help to explain the high incidence of metabolic diseases in individuals exposed to light at night.

Original languageEnglish (US)
Article number122
JournalFrontiers in Endocrinology
Volume9
Issue numberMAR
DOIs
StatePublished - Mar 27 2018

Fingerprint

Melatonin
Leptin
Fasting
Eating
Body Weight
STAT3 Transcription Factor
Hyperphagia
Peptides
Brown Adipose Tissue
Neuropeptide Y
Metabolic Diseases
Adiposity
Energy Intake
Vasoconstriction
Drinking Water
Energy Metabolism
Hypothalamus
Tail
Wistar Rats
Homeostasis

Keywords

  • Brown adipose tissue
  • Feeding behavior
  • Leptin resistance
  • Melatonin
  • Overweight
  • Pinealectomy
  • Signal-transducer and activator of transcription 3
  • Thermogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Buonfiglio, D., Parthimos, R., Dantas, R., Silva, R. C., Gomes, G., Andrade-Silva, J., ... Cipolla-Neto, J. (2018). Melatonin absence leads to long-term leptin resistance and overweight in rats. Frontiers in Endocrinology, 9(MAR), [122]. https://doi.org/10.3389/fendo.2018.00122

Melatonin absence leads to long-term leptin resistance and overweight in rats. / Buonfiglio, Daniella; Parthimos, Rafaela; Dantas, Rosana; Silva, Raysa Cerqueira; Gomes, Guilherme; Andrade-Silva, Jéssica; Ramos-Lobo, Angela; Amaral, Fernanda Gaspar; Matos, Raphael; Sinésio, José; Motta-Teixeira, Lívia Clemente; Donato, José; Reiter, Russel J; Cipolla-Neto, José.

In: Frontiers in Endocrinology, Vol. 9, No. MAR, 122, 27.03.2018.

Research output: Contribution to journalArticle

Buonfiglio, D, Parthimos, R, Dantas, R, Silva, RC, Gomes, G, Andrade-Silva, J, Ramos-Lobo, A, Amaral, FG, Matos, R, Sinésio, J, Motta-Teixeira, LC, Donato, J, Reiter, RJ & Cipolla-Neto, J 2018, 'Melatonin absence leads to long-term leptin resistance and overweight in rats', Frontiers in Endocrinology, vol. 9, no. MAR, 122. https://doi.org/10.3389/fendo.2018.00122
Buonfiglio D, Parthimos R, Dantas R, Silva RC, Gomes G, Andrade-Silva J et al. Melatonin absence leads to long-term leptin resistance and overweight in rats. Frontiers in Endocrinology. 2018 Mar 27;9(MAR). 122. https://doi.org/10.3389/fendo.2018.00122
Buonfiglio, Daniella ; Parthimos, Rafaela ; Dantas, Rosana ; Silva, Raysa Cerqueira ; Gomes, Guilherme ; Andrade-Silva, Jéssica ; Ramos-Lobo, Angela ; Amaral, Fernanda Gaspar ; Matos, Raphael ; Sinésio, José ; Motta-Teixeira, Lívia Clemente ; Donato, José ; Reiter, Russel J ; Cipolla-Neto, José. / Melatonin absence leads to long-term leptin resistance and overweight in rats. In: Frontiers in Endocrinology. 2018 ; Vol. 9, No. MAR.
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AU - Gomes, Guilherme

AU - Andrade-Silva, Jéssica

AU - Ramos-Lobo, Angela

AU - Amaral, Fernanda Gaspar

AU - Matos, Raphael

AU - Sinésio, José

AU - Motta-Teixeira, Lívia Clemente

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