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Nutrients
Volume 16
Issue 1
10.3390/nu16010038
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Article

GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol

by
Kotoko Arisawa
1,2,
Ayumi Matsuoka
2,
Natsuki Ozawa
2,
Tomoko Ishikawa
3,4,
Ikuyo Ichi
3,5 and
Yoko Fujiwara
2,3,*
1
Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8577, Japan
2
Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo 112-8610, Japan
3
Institute for Human Life Science, Ochanomizu University, Tokyo 112-8610, Japan
4
Department of Human Nutrition, Seitoku University, Chiba 271-8555, Japan
5
Natural Science Division, Faculty of Core Research, Ochanomizu University, Tokyo 112-8610, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2024, 16(1), 38; https://doi.org/10.3390/nu16010038
Submission received: 23 October 2023 / Revised: 6 December 2023 / Accepted: 19 December 2023 / Published: 21 December 2023
(This article belongs to the Special Issue Dietary Polyphenols and Metabolic Diseases)
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Abstract

We previously reported that piceatannol (PIC) had an anti-obesity effect only in ovariectomized (OVX) postmenopausal obesity mice. PIC was found to induce the phosphorylation of hormone-sensitive lipase (pHSL) in OVX mice. To elucidate the mechanism by which PIC activates HSL, we investigated the effect of PIC using 3T3-L1 adipocytes. PIC induced HSL phosphorylation at Ser563 in 3T3-L1 cells, as in vivo experiments showed. pHSL (Ser563) is believed to be activated through the β-adrenergic receptor (β-AR) and protein kinase A (PKA) pathways; however, the addition of a selective inhibitor of β-AR did not inhibit the effect of PIC. The addition of a PKA inhibitor with PIC blocked pHSL (Ser563), suggesting that the effects are mediated by PKA in a different pathway than β-AR. The addition of G15, a selective inhibitor of the G protein-coupled estrogen receptor (GPER), reduced the activation of HSL by PIC. Furthermore, PIC inhibited insulin signaling and did not induce pHSL (Ser565), which represents its inactive form. These results suggest that PIC acts as a phytoestrogen and phosphorylates HSL through a novel pathway that activates GPER and its downstream PKA, which may be one of the inhibitory actions of PIC on fat accumulation in estrogen deficiency.
Keywords: piceatannol; hormone-sensitive lipase; adipocyte; lipolysis; G protein-coupled estrogen receptor (GPER) piceatannol; hormone-sensitive lipase; adipocyte; lipolysis; G protein-coupled estrogen receptor (GPER)

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MDPI and ACS Style

Arisawa, K.; Matsuoka, A.; Ozawa, N.; Ishikawa, T.; Ichi, I.; Fujiwara, Y. GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol. Nutrients 2024, 16, 38. https://doi.org/10.3390/nu16010038

AMA Style

Arisawa K, Matsuoka A, Ozawa N, Ishikawa T, Ichi I, Fujiwara Y. GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol. Nutrients. 2024; 16(1):38. https://doi.org/10.3390/nu16010038

Chicago/Turabian Style

Arisawa, Kotoko, Ayumi Matsuoka, Natsuki Ozawa, Tomoko Ishikawa, Ikuyo Ichi, and Yoko Fujiwara. 2024. "GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol" Nutrients 16, no. 1: 38. https://doi.org/10.3390/nu16010038

APA Style

Arisawa, K., Matsuoka, A., Ozawa, N., Ishikawa, T., Ichi, I., & Fujiwara, Y. (2024). GPER/PKA-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol. Nutrients, 16(1), 38. https://doi.org/10.3390/nu16010038

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