The Elovl3 gene, which putatively encodes for a protein involved in the elongation of saturated and monounsaturated fatty acids in the C20- C24 range, is expressed in murine liver, skin and brown adipose tissue (BAT). In BAT, Elovl3 is dramatically up-regulated during tissue activation in response to cold exposure and functional data imply that ELOVL3 is a critical enzyme for lipid accumulation in brown adipocytes during the early phase of tissue recruitment. The activation of BAT is controlled by sympathetic nerve activity and norepinephrine release. By using primary cultures of brown adipocytes we show here that the induced Elovl3 gene expression is synergistically regulated by norepinephrine and the PPAR ligand rosiglitazone. In addition, the potency of rosiglitazone to induce Elovl3 expression was several orders of magnitude higher than for the PPAR and PPAR ligands, WY-14643 and L165041 respectively. The maximal increase in mRNA level by norepinephrine and rosiglitazone is achieved by induced transcription as well as increased mRNA stability, and the whole process requires novel protein synthesis. We conclude that norepinehrine and PPAR, despite having different roles in brown adipocyte activation and differentiation, co-operate in expanding the intracellular lipid pool by synergistically stimulating Elovl3 expression.