Abstract
BackgroundVarious 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.MethodsMouse 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.ResultsBlockade 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.ConclusionsThe 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.
Highlights
Various inflammatory mediators related to obesity might be closely related to insulin resistance
Effects of LOX inhibitors and B4 (LTB4)-leukotriene receptor (BLT) antagonist on mouse 3T3-L1 preadipocyte differentiation Mouse 3T3-L1 cells can differentiate from fibroblastic cells into mature adipocytes in induction medium for differentiation containing insulin (INS), dexamethasone (DEX), 3-isobutyl-1-methylxanthine (IBMX) and rosiglitazone (ROSI), a specific ligand for peroxisome proliferatoractivated receptor gamma (PPARγ) [13,14]
Similar results were observed with BLT2 small interfering RNA (siRNA) (Figure 4D and E). These results clearly indicated that the leukotriene B4 (LTB4)-BLT signaling pathway accelerates mouse 3T3L1 preadipocyte differentiation, and blockade or knockdown of BLTs leads to the suppression of preadipocyte differentiation
Summary
Various inflammatory mediators related to obesity might be closely related to insulin resistance. Leukotrienes (LTs) are involved in inflammatory reactions. There are few reports regarding the role of LTs in adipocyte differentiation. We investigated the role of leukotriene B4 (LTB4)-leukotriene receptor (BLT) signaling in mouse 3T3-L1 fibroblastic preadipocyte differentiation to mature adipocytes. The incidence of obesity and associated metabolic syndrome has dramatically increased. High caloric western-style foods are believed to be the main cause of this dramatic increase, other possible risk factors could exist. The involvement of various inflammatory mediators such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) on obesity might be closely related to insulin resistance [1,2,3,4]. One of the most important organs in obesity and insulin
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