Inhibition of ASCT2 is essential in all-trans retinoic acid-induced reduction of adipogenesis in 3T3-L1 cells

Katsuhiko Takahashi,Natsumi Uchida,Chisato Kitanaka,Chiaki Sagara,Masahiko Imai,Noriko Takahashi

doi:10.1016/j.fob.2015.06.012

Katsuhiko Takahashi, Natsumi Uchida + Show 4 more

Open Access

https://doi.org/10.1016/j.fob.2015.06.012

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Journal: FEBS open bio	Publication Date: Jan 1, 2015
Citations: 11	License type: CC BY 4.0

Affiliation: Hoshi University

Abstract

Vitamin A has preventive effects on obesity. All-trans retinoic acid (ATRA), the active form of vitamin A, inhibits lipid accumulation in 3T3-L1 cells in an experimental adipogenesis model. We found that ATRA suppressed up-regulation of the amino acid transporter, Asct2, in adipogenerating 3T3-L1 cells. We observed that Asct2 was up-regulated at 1day after adipogenesis stimuli. The Asct2 inhibitor l-γ-glutamyl-p-nitroanilide (GPNA) decreased lipid accumulation. Glutamine-free conditions also suppressed adipogenesis. Suppression of adipogenesis by ATRA may be through Asct2 reduction. These results indicate that Asct2 could be a target for obesity prevention and treatment.

Highlights

Obesity is the leading risk for the development of type 2 diabetes mellitus, hypertension and cardiovascular disease
Several reports have shown that Asct2 transcripts are detected in adipose tissues and that insulin up-regulates Asct2 expression in adipogenesis-stimulated 3T3-L1 cells [16,17]
Since we hypothesized that all-trans retinoic acid (ATRA) could potentially suppress 3T3-L1 adipogenesis through Asct2 down-regulation, we added ATRA into the culture medium of DIM-stimulated 3T3-L1 cells to examine the effects of ATRA on the adipogenesis

Summary

Introduction

Obesity is the leading risk for the development of type 2 diabetes mellitus, hypertension and cardiovascular disease. Experiments have shown that molecular mechanisms of adipogenesis form a link between obesity and insulin resistance [1]. Vitamin A is an important nutrient that has multiple biological functions that affect vision, embryonic development, reproduction, and immune function [2,3,4]. The bioactive form of vitamin A is all-trans retinoic acid (ATRA); a nutrient derivative with many remarkable effects on adipocyte biology affecting preadipocyte survival, and adipogenesis in preadipocyte clonal cell lines [5,6]. Several reports have indicated that various adipogenic signaling pathways are involved in the ATRA-dependent regulation of adipogenesis [6,7,8,9,10,11,12]

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