A Co-Drug of Butyric Acid Derived from Fermentation Metabolites of the Human Skin Microbiome Stimulates Adipogenic Differentiation of Adipose-Derived Stem Cells: Implications in Tissue Augmentation

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• 作者：Yanhan Wang¹ ; Lingjuan Zhang¹ ; Jinghua Yu² ; Stephen Huang³ ; Zhenping Wang¹ ; Kimberly Ann Chun¹ ; Tammy Ling Lee¹ ; Ying-Tung Chen⁴ ; Richard L. Gallo¹ ; Chun-Ming Huang¹ ; ⁵ ; ^{chunming@ucsd.edu}
• 关键词：ADSC ; adipose-derived stem cell ; BA-DEG-BA ; butyric acid 2-(2-butyryloxyethoxy) ethyl ester ; CCK-8 ; cell counting kit-8 ; CFSE ; carboxyfluorescein succinimidyl ester ; DEG ; diethylene glycol ; HDAC ; histone deacetylase ; ICR ; Institute of Cancer Research ; NMR ; nuclear magnetic resonance ; PPAR-γ ; peroxisome proliferator-activated receptor gamma ; SCFA ; short-chain fatty acid ; siRNA ; small interfering RNA ; 16S rRNA ; 16S ribosomal RNA
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：46-56
• 全文大小：3616 K
• 卷排序：137

文摘

We show that Staphylococcus epidermidis, a commensal bacterium in the human skin microbiome, produces short-chain fatty acids by glycerol fermentation that can induce adipogenesis. Although the antimicrobial and anti-inflammatory activities of short-chain fatty acids have been previously well characterized, little is known about the contribution of short-chain fatty acids to the adipogenic differentiation of adipose-derived stem cells (ADSCs). We show that ADSCs differentiated into adipocytes and accumulated lipids in the cytoplasm when cultured with butyric acid, a principal short-chain fatty acid in the fermentation metabolites of S. epidermidis. Additionally, a co-drug, butyric acid 2-(2-butyryloxyethoxy) ethyl ester (BA-DEG-BA), released active butyric acid when it was intradermally injected into mouse ears and induced ADSC differentiation, characterized by an increased expression of cytoplasmic lipids and perilipin A. The BA-DEG-BA–induced adipogenic differentiation was mediated via peroxisome proliferator-activated receptor gamma. Furthermore, intradermal injection of ADSCs along with BA-DEG-BA into mouse ears markedly enhanced the adipogenic differentiation of ADSCs, leading to dermal augmentation. Our study introduces BA-DEG-BA as an enhancer of ADSC adipogenesis and suggests an integral interaction between the human skin microbiome and ADSCs.