Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic connexin 43

Eun Roh, Jae Woo Park, Gil Myoung Kang, Chan Hee Lee, Hong Dugu, So Young Gil, Do Kyeong Song, Hyo Jin Kim, Gi Hoon Son, Rina Yu, Min Seon Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Background: Nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 is an important regulator of hypothalamic neuronal function. Thus, an adequate hypothalamic NAD content is critical for maintaining normal energy homeostasis. Methods: We investigated whether NAD supplementation increases hypothalamic NAD levels and affects energy metabolism in mice. Furthermore, we investigated the mechanisms underlying the effects of exogenous NAD on central metabolism upon entering the hypothalamus. Results: Central and peripheral NAD administration suppressed fasting-induced hyperphagia and weight gain in mice. Extracellular NAD was imported into N1 hypothalamic neuronal cells in a connexin 43-dependent and CD73-independent manner. Consistent with the in vitro data, inhibition of hypothalamic connexin 43 blocked hypothalamic NAD uptake and NAD-induced anorexia. Exogenous NAD suppressed NPY and AgRP transcriptional activity, which was mediated by SIRT1 and FOXO1. Conclusions: Exogenous NAD is effectively transported to the hypothalamus via a connexin 43-dependent mechanism and increases hypothalamic NAD content. Therefore, NAD supplementation is a potential therapeutic method for metabolic disorders characterized by hypothalamic NAD depletion.

Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalMetabolism: Clinical and Experimental
StatePublished - Nov 2018

Bibliographical note

Funding Information:
This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT ( 2013M3C7A1056024 , 2015M3A9E7029177 , 2017R1A2B3007123 ) and the Asan Institute for Life Science ( 17-326 ).

Publisher Copyright:
© 2018 Elsevier Inc.


  • Connexin 43
  • Energy metabolism
  • Hypothalamus
  • NAD
  • Supplement


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