P-coumaric acid enhances hypothalamic leptin signaling and glucose homeostasis in mice via differential effects on AMPK activation

Linh V. Nguyen, Khoa D.A. Nguyen, Chi Thanh Ma, Quoc Thai Nguyen, Huong Th Nguyen, Dong Joo Yang, Trung Le Tran, Ki Woo Kim, Khanh V. Doan

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

AMP-activated protein kinase (AMPK) plays a crucial role in the regulation of energy homeostasis in both peripheral metabolic organs and the central nervous system. Recent studies indicated that p-Coumaric acid (CA), a hydroxycinnamic phenolic acid, potentially activated the peripheral AMPK pathway to exert beneficial effects on glucose metabolism in vitro. However, CA’s actions on central AMPK activity and whole-body glucose homeostasis have not yet been in-vestigated. Here, we reported that CA exhibited different effects on peripheral and central AMPK activation both in vitro and in vivo. Specifically, while CA treatment promoted hepatic AMPK acti-vation, it showed an inhibitory effect on hypothalamic AMPK activity possibly by activating the S6 kinase. Furthermore, CA treatment enhanced hypothalamic leptin sensitivity, resulting in increased proopiomelanocortin (POMC) expression, decreased agouti-related peptide (AgRP) expression, and reduced daily food intake. Overall, CA treatment improved blood glucose control, glucose tol-erance, and insulin sensitivity. Together, these results suggested that CA treatment enhanced hy-pothalamic leptin signaling and whole-body glucose homeostasis, possibly via its differential effects on AMPK activation.

Original languageEnglish
Article number1431
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume22
Issue number3
DOIs
Publication statusPublished - 2021 Feb 1

Bibliographical note

Funding Information:
This work was supported by the Tan Tao University (TTU) Foundation for Science and Technology Development under grant number, TTU.RS.19.305.024 (to K.V.D) and by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number, NAFOSTED 108.05-2019.01 (to C.-T.M). This work was also supported by the National Research Foundation (NRF), Korea, 2020M3E5E2038221 (to K.W.K).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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