Nutrients regulate metabolic fluxes and homeostasis through transcriptional and translational control of enzyme concentrations and allosteric modulation of enzyme activity. Dietary ω-3 polyunsaturated fatty acids (PUFAs) have been shown to exert a variety of beneficial health effects such as reducing adiposity and increasing insulin sensitivity in rodents. It is now clear that PUFAs regulate fundamental adipose cell and liver functions through modulation of activity and abundance of key transcription factors that act as nutrient sensors, including peroxisome proliferator-activated receptors (PPAR⍺/δ/γ), sterol regulatory element binding proteins (SREBP-1/2), and liver X receptors (LXR⍺/β). However, in the state of obesity, where adipose tissue shows elevated storage of triglycerides, many lipogenic genes that are essential for adipose cell function including PPARγ, SREBP-1c, CCAAT-enhancer binding protein ⍺ and stearoyl-CoA desaturase-1 are downregulated, apparently due to desensitization of the very same crucial nutrient sensors. This chapter will summarize recent studies of PUFA- and obesity-induced changes in gene expression in white adipose tissue.