Inhibition of adipogenesis in 3T3-L1 cells and suppression of abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice after downregulation of hyaluronic acid

Int J Obes (Lond). 2014 Aug;38(8):1035-43. doi: 10.1038/ijo.2013.202. Epub 2013 Oct 31.


Objective: Adipogenesis can be spatially and temporally regulated by extracellular matrix (ECM). We hypothesized that the regulation of hyaluronic acid (HA), a component of the ECM, can affect adipogenesis in fat cells. The effects of HA on adipogenesis were investigated in vitro in 3T3-L1 cells and in vivo in high-fat diet-feeding C57BL/6J mice.

Methods: We investigated the effects of HA by degradation of pre-existing or synthesized HA and artificial inhibition of HA synthesis in adipogenesis.

Results: In vitro adipogenesis in 3T3-L1 cells was inhibited by treating them with exogenous hyaluronidase (HYAL) and with 4-methylumbelliferone, which inhibited the synthesis of HA in a concentration-dependent manner. In vivo, abdominal fat accumulation in high-fat diet-feeding C57BL/6J mice was suppressed by exogenous HYAL 10(4) IU injections, which was associated with reduction of lipid accumulation in liver and increase of insulin sensitivity.

Conclusion: Changes in the ECM such as accumulation of high molecular weight of HA by HAS and degradation of HA by endogenous HYAL were essential for adipogenesis both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells / metabolism*
  • Abdominal Fat / metabolism*
  • Adipogenesis*
  • Animals
  • Cell Differentiation
  • Diet, High-Fat*
  • Down-Regulation
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation
  • Hyaluronic Acid / metabolism*
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / prevention & control
  • Obesity / physiopathology
  • Obesity / prevention & control


  • Hyaluronic Acid