Critical role of leukotriene B4 receptor signaling in mouse 3T3-L1 preadipocyte differentiation.
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.
Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Suita, Osaka 565-0871, Japan. khirata@dent.osaka-u.ac.jp
Kae
K
Hirata
Koichiro
K
Wada
Yuka
Y
Murata
Atsushi
A
Nakajima
Takashi
T
Yamashiro
Yoshinori
Y
Kamisaki
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007975:Leukotriene B4 / Q000235:genetics / Q000378:metabolism*; D008084:Lipoxygenase / Q000235:genetics / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage; D051379:Mice; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D016859:Lipoxygenase Inhibitors; D034741:RNA, Small Interfering; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D008084:Lipoxygenase