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

doi:10.3390/ijms22031431

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

8 Citations (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 language	English
Article number	1431
Pages (from-to)	1-13
Number of pages	13
Journal	International journal of molecular sciences
Volume	22
Issue number	3
DOIs	https://doi.org/10.3390/ijms22031431
Publication status	Published - 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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@article{9badec4402994170a6754efc9b18e0a3,

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

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{\textquoteright}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.",

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

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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Nguyen, Linh V.

AU - Nguyen, Khoa D.A.

AU - Ma, Chi Thanh

AU - Nguyen, Quoc Thai

AU - Nguyen, Huong Th

AU - Yang, Dong Joo

AU - Tran, Trung Le

AU - Kim, Ki Woo

AU - Doan, Khanh V.

N1 - 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.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

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

Abstract

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