Schmidt A, Vogel R L, Witherup K M, Rutledge S J, Pitzenberger S M, Adam M, Rodan G A
Department of Bone Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Lipids. 1996 Nov;31(11):1115-24. doi: 10.1007/BF02524285.
The nuclear hormone receptors NUC-1 (PPAR delta) and PPAR alpha are members of the peroxisome proliferator-activated receptor (PPAR) family. The members of this receptor family are activated by agents that stimulate peroxisome proliferation, free fatty acids, prostaglandin 12 metabolites, and agents considered for the therapy of insulin-independent diabetes mellitus. To identify putative physiological agents that activate NUC-1, we tested the ability of acetone extracts of various rat tissues to activate the transcription of an MMTV-luciferase reporter gene, via a GR/NUC-1 hybrid receptor. GR/NUC-1 contains the ligand binding region of the NUC-1 receptor and the DNA binding domain of the glucocorticoid receptor. Using this assay, we found stimulatory activity in the pancreas, which upon purification and characterization was identified as methyl-palmitate, known to be enriched in pancreatic lipids. In addition, we determined that ethyl esters of palmitic and oleic acids are also potent activators of this receptor. Thus, fatty acid ester formation may control the cellular concentrations of fatty acids, and acyl-ester formation may play a role in the control of metabolic pathways and the activation of the PPAR.
核激素受体NUC-1（PPARδ）和PPARα是过氧化物酶体增殖物激活受体（PPAR）家族的成员。该受体家族的成员可被刺激过氧化物酶体增殖的物质、游离脂肪酸、前列腺素12代谢产物以及用于治疗非胰岛素依赖型糖尿病的药物激活。为了鉴定激活NUC-1的假定生理物质，我们通过GR/NUC-1杂交受体测试了各种大鼠组织的丙酮提取物激活MMTV-荧光素酶报告基因转录的能力。GR/NUC-1包含NUC-1受体的配体结合区域和糖皮质激素受体的DNA结合结构域。使用该检测方法，我们在胰腺中发现了刺激活性，经纯化和鉴定后确定为甲基棕榈酸酯，已知其在胰腺脂质中含量丰富。此外，我们还确定棕榈酸和油酸的乙酯也是该受体的有效激活剂。因此，脂肪酸酯的形成可能控制脂肪酸的细胞浓度，而酰基酯的形成可能在代谢途径的控制和PPAR的激活中发挥作用。
