All-trans retinoic acid induces mitochondria-mediated apoptosis of human adipose-derived stem cells and affects the balance of the adipogenic differentiation

Schweich, Laynna de Carvalho; Oliveira, Edwin José Torres de; Pesarini, João Renato; Hermeto, Larissa Corrêa; Camassola, Melissa; Nardi, Nance Beyer; Brochado, Themis Maria Milan; Antoniolli-Silva, Andréia Conceição Milan Brochado; Oliveira, Rodrigo Juliano

doi:10.1016/j.biopha.2017.11.087

Cited by 18 publications

(12 citation statements)

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“…e inhibitory effect of atRA on adipogenesis has been confirmed in many studies [18,19,29,30]. We repeated a previous experiment with 5 μmol/L atRA in BMSCs.…”

Section: Overexpression Of Fra1 and Atra Treatment Could Block Bmsc Dsupporting

confidence: 59%

All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

Xie

Zou

Chen

et al. 2020

International Journal of Endocrinology

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Obesity, caused by an increased number and volume of adipocytes, is a global epidemic that seriously threatens human health. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into adipocytes. All-trans retinoic acid (atRA, the active form of vitamin A) inhibits the adipogenic differentiation of BMSCs through its receptor RARG. The expression level of FRA1 (FOS like 1, AP-1 transcription factor subunit) in atRA-treated BMSCs increased, suggesting that atRA-mediated inhibition of BMSCs adipogenesis involves FRA1. BMSCs were transfected with adenovirus overexpressing Fra1 (ad-fra1) or silenced for Fra1 (si-fra1) and then treated with atRA. BMSCs treated with atRA and treated with ad-fra1 showed decreased mRNA and protein levels of key adipogenic genes (Pparg2, Cebpa) and adipogenesis-associated genes (Cd36, Fabp, Lpl, and Plin); atRA had a stronger inhibitory effect on adipogenesis compared with that in the ad-fra1 group. Adipogenic gene expression in Fra1-silenced BMSCs was significantly upregulated. Compared with that in the atRA group, the si-fra1 + atRA also upregulated adipogenic gene expression. However, compared with si-fra1, si-fra1 + atRA significantly inhibited adipogenic differentiation. Chromatin immunoprecipitation showed that RARG directly regulates Fra1 and FRA1 directly regulates Pparg2 and Cebpa. The results supported the conclusion that atRA inhibits BMSC adipogenesis partially through the RARG-FRA1-PPARG2 or the CEBPA axis or both. Thus, vitamin A might be used to treat obesity and its related diseases.

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“…e inhibitory effect of atRA on adipogenesis has been confirmed in many studies [18,19,29,30]. We repeated a previous experiment with 5 μmol/L atRA in BMSCs.…”

Section: Overexpression Of Fra1 and Atra Treatment Could Block Bmsc Dsupporting

confidence: 59%

All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

Xie

Zou

Chen

et al. 2020

International Journal of Endocrinology

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“…Other studies exploring retinoic acid effects on human adipose-derived stem cells increasing the frequency of Sub-G1 cells and decreased it is G1, establishing where in the cell cycle retinoic acid acts (de Carvalho Schweich et al, 2017). Gene expression data obtained for treated cells suggested that retinoic acid treatment leads to mitochondrial membrane permeabilization and the consequent release of proapoptotic factors including BAK and BAX.…”

Section: B Vitamin a Vitamin A-related Proteins And Adipose Biologymentioning

confidence: 96%

Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders

Blaner

2019

Pharmacology & Therapeutics

200

174

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Much evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported associations. However, a number of proteins involved in vitamin A metabolism, including retinolbinding protein 4 (RBP4) and aldehyde dehydrogenase 1A1 (ALDH1A1, alternatively known as retinaldehyde dehydrogenase 1 or RALDH1), have also been identified as being associated with metabolic disease. Some of the reported effects of these vitamin A-related proteins are proposed to be independent of their roles in assuring normal retinoic acid homeostasis. This review will consider both human observational data as well as published data from molecular studies undertaken in rodent models and in cells in culture. The primary focus of the review will be on the effects that vitamin A per se and proteins involved in vitamin A metabolism have on adipocytes, adipose tissue biology, and adipose-related disease, as well as on early stage liver disease, including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

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“…Cell viability assay. The cytotoxic potential of AMS35AA was evaluated by the MTT colorimetric test performed as described by Pesarini et al (2017) and Schweich et al (2017), with modifications (6, 7). Cells were seeded at a density of 3×10 3 in 96 well culture plates in a supplemented DMEM medium and incubated in 5% CO 2 atmosphere at 37˚C for 24 h for adherence and stabilization.…”

Section: Methodsmentioning

confidence: 99%

“…Lysis of DNA was performed using 100 μl of lysis solution (50 μg/l PI, 0.1% sodium citrate, 0.1% Triton X-100), and incubated on ice in the dark for 30 min. Fluorescence intensity (from 10,000 cells) was immediately analyzed by flow cytometry (BD Accuri™ C6, Becton Dickinson, Franklin Lakes, EUA) with 488-nm laser excitation (7).…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of the Antitumor Potential of the Resorcinolic Lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in Breast Cancer Cells

et al. 2018

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All-trans retinoic acid induces mitochondria-mediated apoptosis of human adipose-derived stem cells and affects the balance of the adipogenic differentiation

Cited by 18 publications

References 50 publications

All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

All-Trans Retinoic Acid Inhibits Bone Marrow Mesenchymal Stem Cell Commitment to Adipocytes via Upregulating FRA1 Signaling

Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders

Evaluation of the Antitumor Potential of the Resorcinolic Lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one in Breast Cancer Cells

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