Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile

Overview

Journal JACC Basic Transl Sci

Date 2023 Oct 4

PMID 37791312

Authors

Masayuki Takano

Hidekazu Kondo

Taisuke Harada

Masaki Takahashi

Yumi Ishii

Hirochika Yamasaki

Tong Shan

Kumiko Akiyoshi

Takashi Shuto

Yasushi Teshima

Tomoyuki Wada

Kunio Yufu

Hidenori Sako

Hirofumi Anai

Shinji Miyamoto

Naohiko Takahashi

Affiliations

Soon will be listed here.

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce epicardial adipose tissue (EAT) in humans, enhancing cardioprotective effects on heart failure and atrial fibrillation. We investigated the direct effect of the SGLT2 inhibitor empagliflozin on human primary epicardial adipocytes and preadipocytes. SGLT2 is primarily expressed in human preadipocytes in the EAT. The expression levels of SGLT2 significantly diminished when the preadipocytes were terminally differentiated. Adipogenesis of preadipocytes was attenuated by empagliflozin treatment without affecting cell proliferation. The messenger RNA levels and secreted protein levels of interleukin 6 and monocyte chemoattractant protein 1 were significantly decreased in empagliflozin-treated adipocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes pretreated with or without empagliflozin revealed that empagliflozin significantly suppressed reactive oxygen species. messenger RNA expression in human EAT showed significant clinically relevant associations. Empagliflozin suppresses human epicardial preadipocyte differentiation/maturation, likely inhibiting epicardial adipogenesis and improving the paracrine secretome profile of EAT, particularly by regulating expression.

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