Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Gper/Pka-Dependent Enhancement of Hormone-Sensitive Lipase Phosphorylation in 3T3-L1 Adipocytes by Piceatannol.

Version 1 : Received: 23 October 2023 / Approved: 24 October 2023 / Online: 24 October 2023 (07:50:51 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

Piceatannol (PIC), a natural analog of resveratrol, has various biological functions. We previously reported that PIC had an anti-obesity effect only in ovariectomized mice. While ovariectomized mice have low phosphorylation levels of hormone-sensitive lipase (pHSL) at Ser563, we found that PIC increased those levels. Here, we investigated the effect of PIC using 3T3-L1 adipocytes to clarify the mechanism by which PIC activates HSL. First, PIC was confirmed to induce 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) pathway; however, the addition of a selective inhibitor of β-AR did not inhibit the effect of PIC. The addition of PKA inhibitor with PIC blocked pHSL (Ser563), suggesting that PIC’s effects are mediated by PKA from a different pathway than β-AR. The addition of G15, a selective inhibitor of the G protein-coupled estrogen receptor (GPER), lowered HSL activation by PIC. Furthermore, PIC inhibited insulin signaling and did not induce pHSL (Ser565), which represents its inactive form. This study is the first to suggest that the GPER pathway might regulate HSL activation in adipocytes.

Keywords

piceatannol; hormone-sensitive lipase; adipocyte; lipolysis; G protein coupled-estrogen receptor (GPER)

Subject

Biology and Life Sciences, Life Sciences

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