The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells

Early Hum Dev. 2013 Sep;89(9):713-9. doi: 10.1016/j.earlhumdev.2013.05.002. Epub 2013 Jun 10.

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.

Aims: We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes.

Study design and subjects: 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.

Keywords: Adipocyte; Arachidonic acid; Human milk; Infant formula; Lipid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Dexamethasone / pharmacology
  • Female
  • Humans
  • Infant
  • Infant Formula / pharmacology
  • Insulin / pharmacology
  • Lipids / pharmacology*
  • Mice
  • Milk, Human / chemistry*
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Insulin
  • Lipids
  • Tissue Inhibitor of Metalloproteinase-3
  • Dexamethasone