Norepinephrine and rosiglitazone synergistically induce Elov13 expression in brown adipocytes

作者：Jorgensen Johanna A; Zadravec Damir; Jacobsson Anders^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2007, 293(5): E1159-E1168.

DOI：10.1152/ajpendo.00213.2007

• fatty acid synthesis
• fatty acid elongation
• very long-chain fatty acids
• lipid metabolism
• peroxisome proliferator-activated receptor-gamma

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 upregulated 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 peroxisome proliferator-activated receptor ( PPAR) gamma ligand rosiglitazone. In addition, the potency of rosiglitazone to induce Elovl3 expression was several orders of magnitude higher than for the PPAR alpha and PPAR delta ligands WY-14643 and L-165041, 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 gamma, despite having different roles in brown adipocyte activation and differentiation, cooperate in expanding the intracellular lipid pool by synergistically stimulating Elovl3 expression.

• 出版日期2007-11