Expression of the ANGPTL4 gene, encoding Angiopoietin-related protein 4, also known as PPARG angiopoietin related (PGAR), is positively regulated by the PPARG:RXRA heterodimer and MLL3/MLL4 histone methyltransferases. Based on studies in mouse preadipocyte cell line 3T3-L1, ANGTPL4 expression is rapidly induced upon treatment with PPARG agonists (Yoon et al. 2000, Allen et al. 2006, Bhalla et al. 2011) in the absence of protein synthesis (Yoon et al. 2000). ANGTPL4 mRNA is highly expressed in human white fat and placenta (Yoon et al. 2000). Angptl4 expression in mouse white fat upon treatment with the PPARG agonist rosiglitazone leads to enhanced angiogenesis, which is likely required for adipose tissue growth (Gealekman et al. 2008). By microarray-based gene expression analysis in primary human white adipocytes undergoing browning, the mRNA level of ANGPTL4 is significantly increased upon treatment with the PPARG agonist rosiglitazone (Barquissau et al. 2016: supplementary information, Table S3). Expression of the Angptl4 gene is severely reduced in differentiating mouse brown preadipocytes expressing histone H3.3 K4M mutant or Kmt2c (Mll3) and Kmt2d (Mll4) with deleted SET domains (Jang et al. 2019: RNA-seq, supplementary information). RNA Pol II occupancy at the Angptl4 gene promoter is increased in response to PPARG agonists (Nielsen et al. 2008). Pparg-mediated upregulation of Angptl4 secretion from mouse white fat tissue was shown to specifically promote proliferation of glucagon-secreting alpha-cells of the endocrine pancreas (Ben-Zvi et al. 2015). In mice, it was shown that ANGPTL4 is involved in regulation of lipid metabolism by inhibiting lipoprotein lipase (LPL) responsible for the clearance of lipids from the bloodstream, therefore leading to increased blood levels of plasma triglycerides (TG) and fatty acids (Yoshida et al. 2002).