Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes.

Dae-Kun Lee,Hae-Dong Jang

doi:10.3390/ijms22116096

Abstract

The objective of this study was to investigate molecular mechanisms underlying the ability of carnosic acid to attenuate an early increase in reactive oxygen species (ROS) levels during MDI-induced adipocyte differentiation. The levels of superoxide anion and ROS were determined using dihydroethidium (DHE) and 2′-7′-dichlorofluorescin diacetate (DCFH-DA), respectively. Both superoxide anion and ROS levels peaked on the second day of differentiation. They were suppressed by carnosic acid. Carnosic acid attenuates the translation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4), p47phox, and p22phox, and the phosphorylation of nuclear factor-kappa B (NF-κB) and NF-κB inhibitor (IkBa). The translocation of NF-κB into the nucleus was also decreased by carnosic acid. In addition, carnosic acid increased the translation of heme oxygenase-1 (HO-1), γ–glutamylcysteine synthetase (γ-GCSc), and glutathione S-transferase (GST) and both the translation and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Taken together, these results indicate that carnosic acid could down-regulate ROS level in an early stage of MPI-induced adipocyte differentiation by attenuating ROS generation through suppression of NF-κB-mediated translation of Nox4 enzyme and increasing ROS neutralization through induction of Nrf2-mediated translation of phase II antioxidant enzymes such as HO-1, γ-GCS, and GST, leading to its anti-adipogenetic effect.

Highlights

Obesity is a chronic disease directly caused by abnormal increases in both the size and number of adipocytes
To determine whether superoxide anion and reactive oxygen species (ROS) levels in the early stage of adipocyte differentiation might be down-regulated by carnosic acid, superoxide anion and ROS levels at day two of adipocyte differentiation were analyzed
Carnosic acid at 10–20 μM attenuated the early increase in both superoxide anion and ROS levels were significantly (p < 0.001) induced by an MDI hormone mixture (Figure 1C,D)

Summary

Introduction

Obesity is a chronic disease directly caused by abnormal increases in both the size and number of adipocytes. Several types of cells, including pre-adipocytes, mature adipocytes, fibroblasts, pericytes, macrophages, neutrophils, lymphocytes, endothelial cells, and adipose stem cells, exist [1]. Pre-adipocyte originating from adipose stem cells are known to be differentiated into adipocytes. This process is called adipogenesis [2]. Several strategies such as reducing energy/food intake, increasing energy expenditure, inhibiting adipogenesis, inhibiting lipogenesis, and increasing lipolysis and fat oxidation have been proposed [3]. Among them, decreasing adipogenesis might be one of the better strategies for preventing obesity caused by enhanced adipogenesis [4]

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