1. Carvacrol reduces adipogenic differentiation by modulating autophagy and ChREBP expression.
- Author
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Spalletta S, Flati V, Toniato E, Di Gregorio J, Marino A, Pierdomenico L, Marchisio M, D'Orazi G, Cacciatore I, and Robuffo I
- Subjects
- 3T3-L1 Cells, Adipocytes drug effects, Adipocytes physiology, Adipogenesis physiology, Animals, Autophagy physiology, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Cell Line, Cymenes, Drug Evaluation, Preclinical, Gene Expression Regulation drug effects, Humans, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells physiology, Mice, Monoterpenes therapeutic use, Obesity etiology, Primary Cell Culture, Wharton Jelly cytology, Adipogenesis drug effects, Autophagy drug effects, Cell Differentiation drug effects, Monoterpenes pharmacology, Nuclear Proteins metabolism, Obesity drug therapy, Transcription Factors metabolism
- Abstract
Objective: Obesity is the result of white adipose tissue accumulation where excess of food energy is stored to form triglycerides. De novo lipogenesis (DNL) is the continuous process of new fat production and is driven by the transcription factor ChREBP. During adipogenesis, white adipocytes change their morphology and the entire cell volume is occupied by one large lipid droplet. Recent studies have implicated an essential role of autophagy in adipogenic differentiation, cytoplasmic remodelling and mitochondria reorganization. The phenolic monoterpenoid carvacrol (2-methyl-5-[1-methylethyl]phenol), produced by numerous aromatic plants, has been shown to reduce lipid accumulation in murine 3T3-L1 cells during adipogenic differentiation by modulating genes associated with adipogenesis and inflammation. Therefore, the aim of this study was to evaluate whether carvacrol could affect autophagy and ChREBP expression during adipogenic differentiation., Methods: The study was carried on by using the murine 3T3-L1 and the human WJ-MSCs (Wharton's jelly-derived mesenchymal stem cells) cell lines. Cells undergoing adipogenic differentiation were untreated or treated with carvacrol. Adipogenic differentiation was assessed by analyzing cellular lipid accumulation with Oil-Red O staining and by ultrastructural examination with TEM. Autophagy was evaluated by western immunoblotting of autophagy markers LC3B and p62/SQSTM and by ultrastructural examination of autophagic bodies. Autophagic flux was evaluated by using autophagy inhibitor cloroquine (CQ). ChREBP expression levels was assessed by both western blotting and immunoelectron microscopy and ChREBP activity by analysis of adipogenic target genes expression., Results: We found that carvacrol reduced adipogenic differentiation of about 40% and 30% in, respectively, 3T3-L1 and in WJ-MSCs cells. The effect of carvacrol on adipogenic differentiation correlated with both reduction of autophagy and reduction of ChREBP expression., Conclusion: The results support the notion that carvacrol, through its effect on autophagy (essential for adipocyte maturation) and on ChREBP activity, could be used as a valuable adjuvant to reduce adipogenic differentiation., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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