title: Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue.
abstract: BACKGROUND
  Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are the main products of microbial fermentation in the gut and might mediate some of the effects of gut microbiota and nutrition on development, metabolism, and pathogenesis of obesity and other diseases.
  
  
  OBJECTIVE
  The objective of this study was to determine the effects of SCFAs on adipocyte differentiation and the underlying mechanism.
  
  
  METHODS
  The stromal vascular fraction (SVF) of the porcine subcutaneous fat was used as the preadipocyte model. Adipocyte differentiation was assessed by Oil Red O staining and gene expression analysis of adipocyte markers. Chromatin immunoprecipitation was used to assess the histone acetylation amounts at the peroxisome proliferator-activated receptor γ (PPARG) and CCAAT/enhancer binding protein α (CEBPA) promoters.
  
  
  RESULTS
  Compared with control, propionate and butyrate enhanced the formation of adipocytes by 10-20% and mRNA expression of adipocyte markers by 20-200% in porcine SVF undergoing adipocyte differentiation. Compared with control, short-term treatment of propionate and butyrate enhanced PPARG and CEBPA mRNA expression in porcine SVF by 50-100%. Neither free fatty acid receptor (FFAR) 2 nor FFAR3 mRNA was detectable in porcine SVF before or during differentiation. Neither a cAMP analogue nor an activator of AMP-activated protein kinase (AMPK) affected propionate- or butyrate-enhanced expression of PPARG or CEBPA mRNA. Trichostatin A, a specific inhibitor of histone deacetylases (HDACs), enhanced the formation of adipocytes in porcine SVF by nearly 100% and the expression of PPARG and CEBPA mRNAs by 150% and 50%, respectively. Butyrate increased whereas propionate had no significant effect on histone H3 acetylation at the CEBPA promoter in porcine SVF.
  
  
  CONCLUSIONS
  Propionate and butyrate enhance adipocyte differentiation in porcine SVF. These effects are unlikely mediated through FFAR2, FFAR3, cAMP, or AMPK. The effect of butyrate may be partially mediated by its HDAC inhibitory activity, whereas that of propionate is independent of its HDAC inhibitory activity.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China; and.
authors.forename: Genlai
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China; and yaowen67jp@njau.edu.cn hojiang@vt.edu.
authors.forename: Wen
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA yaowen67jp@njau.edu.cn hojiang@vt.edu.
authors.forename: Honglin
authors.initials: H
authors.lastname: Jiang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000107:Acetylation; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002087:Butyrates / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011422:Propionates / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012263:Ribonucleosides / Q000494:pharmacology; D013552:Swine
chemical_list: D002087:Butyrates; D022762:CCAAT-Enhancer-Binding Proteins; D005232:Fatty Acids, Volatile; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D047495:PPAR gamma; D011422:Propionates; D012333:RNA, Messenger; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C012589:trichostatin A; C011651:acadesine; D055372:AMP-Activated Protein Kinases
keywords: PPAR; adipose tissue; pig; promoter; short chain fatty acids