title: Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages.
abstract: OBJECTIVE
  Paracrine interaction between macrophages and adipocytes in obese visceral fat tissues is thought to be a trigger of chronic inflammation. The immunomodulatory effect of the short chain fatty acid, butyric acid, has been demonstrated. We hypothesize that sodium butyrate (butyrate) attenuates inflammatory responses and lipolysis generated by the interaction of macrophages and adipocytes.
  
  
  METHODS
  Using contact or transwell co-culture methods with differentiated 3T3-L1 adipocytes and RAW264.7 macrophages, we investigated the effects of butyrate on the production of tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and the release of free glycerol, free fatty acids (FFAs) into the medium. We also examined the activity of nuclear factor-kappaB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) in co-cultured macrophages, as well as lipase activity and expression in co-cultured adipocytes.
  
  
  RESULTS
  We found increased production of TNF-α, MCP-1, IL-6, and free glycerol, FFAs in the co-culture medium, and butyrate significantly reduced them. Butyrate inhibited the phosphorylation of MAPKs, the activity of NF-κB in co-cultured macrophages, and suppressed lipase activity in co-cultured adipocytes. Lipase inhibitors significantly attenuated the production of TNF-α, MCP-1 and IL-6 in the co-culture medium as effectively as butyrate. Butyrate suppressed the protein production of adipose triglyceride lipase, hormone sensitive lipase, and fatty acid-binding protein 4 in co-cultured adipocytes. Pertussis toxin, which is known to block GPR41 completely, inhibited the antilipolysis effect of butyrate.
  
  
  CONCLUSIONS
  Butyrate suppresses inflammatory responses generated by the interaction of adipocytes and macrophages through reduced lipolysis and inhibition of inflammatory signaling.
authors.affiliation: Division of Clinical Nutrition, Faculty of Nutrition, Kobe Gakuin University, Japan. oohira@nutr.kobegakuin.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Ohira
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Chikae
authors.initials: C
authors.lastname: Katagiri
authors.forename: Rie
authors.initials: R
authors.lastname: Mamoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Aoyama-Ishikawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Amako
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Makoto
authors.initials: M
authors.lastname: Usami
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018920:Coculture Techniques; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects; D037342:Pertussis Toxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002087:Butyrates; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D037342:Pertussis Toxin; D008049:Lipase