Critical role of leukotriene B4 receptor signaling in mouse 3T3-L1 preadipocyte differentiation

Lipids Health Dis. 2013 Aug 9:12:122. doi: 10.1186/1476-511X-12-122.

Abstract

Background: Various inflammatory mediators related to obesity might be closely related to insulin resistance. Leukotrienes (LTs) are involved in inflammatory reactions. However, there are few reports regarding the role of LTs in adipocyte differentiation. Therefore, we investigated the role of leukotriene B4 (LTB4)-leukotriene receptor (BLT) signaling in mouse 3T3-L1 fibroblastic preadipocyte differentiation to mature adipocytes.

Methods: Mouse 3T3-L1 preadipocytes were treated with lipoxygenase (LOX) inhibitors, BLT antagonist, and small interfering RNA (siRNA) for BLT1 and BLT2 to block the LTB4-BLT signaling pathway, then the adipocyte differentiation such as lipid accumulation and the increase in triglyceride was evaluated.

Results: Blockade of BLT signaling by treatment with a LOX inhibitor or a BLT antagonist suppressed preadipocyte differentiation into mature adipocytes. In addition, knockdown of BLT1 and BLT2 by siRNAs dramatically inhibited differentiation. These results indicate the LTB4-BLT signaling pathway may positively regulate preadipocyte differentiation and be a rate-limiting system to control adipocyte differentiation.

Conclusions: The LTB4-BLT signaling pathway provides a potent regulatory signal that accelerates the differentiation of mouse 3T3-L1 preadipocytes. Further investigations are necessary to confirm the exact role of LTB4 and BLTs signaling pathways in preadipocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Insulin Resistance / genetics
  • Leukotriene B4 / genetics
  • Leukotriene B4 / metabolism*
  • Lipoxygenase / genetics
  • Lipoxygenase / metabolism
  • Lipoxygenase Inhibitors / administration & dosage
  • Mice
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • RNA, Small Interfering
  • Receptors, Leukotriene B4 / genetics
  • Receptors, Leukotriene B4 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Lipoxygenase Inhibitors
  • RNA, Small Interfering
  • Receptors, Leukotriene B4
  • Leukotriene B4
  • Lipoxygenase