title: 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.
abstract: 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.
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Yanhan
authors: Y
authors: Wang
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Lingjuan
authors: L
authors: Zhang
authors: Sanford-Burnham Institute for Medical Research, La Jolla, California, USA.
authors: Jinghua
authors: J
authors: Yu
authors: Surface Bioadvances Incorporated, San Diego, California, USA.
authors: Stephen
authors: S
authors: Huang
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Zhenping
authors: Z
authors: Wang
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Kimberly Ann
authors: KA
authors: Chun
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Tammy Ling
authors: TL
authors: Lee
authors: Nerd SkinCare Incorporated, San Francisco, California, USA.
authors: Ying-Tung
authors: YT
authors: Chen
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.
authors: Richard L
authors: RL
authors: Gallo
authors: Department of Dermatology, School of Medicine, University of California, San Diego, California, USA; Moores Cancer Center, University of California, San Diego, California, USA. Electronic address: chunming@ucsd.edu.
authors: Chun-Ming
authors: CM
authors: Huang
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D002454:Cell Differentiation; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000187:drug effects* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000166:cytology / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D017077:Culture Media, Conditioned; D020148:Butyric Acid