Schematic diagram of the proposed pathway in male mice by which PPARα inhibition of the PASK–SREBP-1 axis reduces lipogenesis, inflammation, and cholesterol esterification. In adipocytes, PPARα inhibits PASK expression and activation of SREBP-1. Typically, the SREBP-1 transcription factor, when activated, is truncated to the mature form, which can bind to sterol response elements (SREs) in gene promoters to control the expression of genes for lipogenesis (stearoyl-coenzyme A desaturase 1 (SCD1) and fatty acid synthase (FAS)) and cholesterol metabolism (Abca1, Abcg1, and Scarb1). The loss of PPARα in adipose tissue causes a significant increase in iNOS, which mediates the switch of macrophage polarity from anti-inflammatory M2 to pro-inflammatory M1. Abbreviations: PPARα, peroxisome proliferator-activated receptor-alpha; SREBP-1, sterol regulatory element-binding protein-1; PASK, Per-Arnt-Sim Kinase; CE, cholesterol ester; SRE, sterol response element.