title: The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.
abstract: BACKGROUND
  The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood.
  
  
  OBJECTIVE
  We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes.
  
  
  METHODS
  3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined.
  
  
  RESULTS
  We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail.
  
  
  CONCLUSIONS
  These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway.
authors.affiliation: Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. yasu627@fc4.so-net.ne.jp
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Rie
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Eiko
authors.initials: E
authors.lastname: Nagata
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Satake
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sano
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushita
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Kitsuta
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakashima
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology*; D051379:Mice; D008895:Milk, Human / Q000737:chemistry*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D007328:Insulin; D008055:Lipids; D019717:Tissue Inhibitor of Metalloproteinase-3; D003907:Dexamethasone
keywords: Adipocyte; Arachidonic acid; Human milk; Infant formula; Lipid