Expression of the FABP4 gene, encoding Fatty acid-binding protein 4, also known as aP2, is positively regulated in fat tissue by the PPARG:RXRA heterodimer and KMT2C (MLL3)/KMT2D (MLL4) histone methyltransferase complexes. Based on a mouse study, the heterodimer of PPARG and RXRA directly stimulates transcription of the FABP4 (aP2) gene by binding to an adipocyte-specific enhancer (Tontonoz et al. 1994). Expression of FABP4 is significantly down-regulated in white adipose tissue (WAT) of Kmt2c (Mll3) delta/delta mice that express H3K4 methyltransferase inactive Kmt2c mutant (Lee et al. 2008). Expression of Fabp4 is completely ablated in Ncoa6-null cells (Qi et al. 2003). Mouse embryonic fibroblasts (MEFs) deficient for Paxip1 (Ptip), an accessory subunit of MLL3 and MLL4 complexes, do not show a defect in Pparg- and ligand-stimulated expression of endogenous Fabp4 (Cho et al. 2009).

Based on a study in MEFs in which Pparg was ectopically expressed, Pparg positively regulates Fabp4 transcription in a ligand-dependent manner (Ge et a. 2008).

Treatment of mouse white preadipocyte cell line 3T3-L1 with PPARG agonists results in increased Fabp4 mRNA levels (Allen et al. 2006, Bhalla et al. 2011).

By microarray-based gene expression analysis in primary human white adipocytes undergoing browning, the mRNA level of FABP4 is significantly increased upon treatment with the PPARG synthetic agonist rosiglitazone (Barquissau et al. 2016: supplementary information, Table S3). In human monocytes, mRNA level of FABP4 is significantly increased upon treatment with the natural PPARG ligand 15d-PGJ2 (Pelton et al. 1999).

In mouse brown preadipocytes expressing histone 3 mutant H3.3 K4M, the expression of Fabp4 is severely reduced (Jang et al. 2019). Deletion of SET domains of Kmt2c and Kmt2d in mouse brown preadipocytes prevents induction of Fabp4 during adipogenesis (Jang et al. 2019).