We investigated the role of leukotriene B-4 (LTB4)-leukotriene receptor (BLT) signaling in preadipocyte differentiation into mature adipocytes. Blockade of BLT signaling by treatment with lipoxygenase inhibitors, a BLT antagonist, and small interfering RNAs for BLTs in human and mouse preadipocytes isolated from adipose tissues showed acceleration of differentiation into mature adipocytes. DNA microarray analysis revealed regulation of transforming growth factor, beta-induced 68 kDa (TGFBI) expression through the BLT signaling pathway during adipocyte differentiation. Knockdown of TGFBI also showed acceleration of preadipocyte differentiation. The LTB4-BLT signaling pathway may negatively regulate preadipocyte differentiation via induction of TGFBI expression as a rate-limiting system to control adipocyte differentiation. (C) 2012 Elsevier Inc. All rights reserved.