Wolins Nathan E, Quaynor Benjamin K, Skinner James R, Tzekov Anatoly, Croce Michelle A, Gropler Matthew C, Varma Vijayalakshmi, Yao-Borengasser Aiwei, Rasouli Neda, Kern Philip A, Finck Brian N, Bickel Perry E
Department of Medicine, 660 S. Euclid Ave., Campus Box 8127, St. Louis, MO 63110, USA.
Diabetes. 2006 Dec;55(12):3418-28. doi: 10.2337/db06-0399.
Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as "OXPAT." Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation, long-chain fatty acid oxidation, and mRNAs associated with oxidative metabolism. Consistent with these observations, OXPAT is induced in mouse adipose tissue, striated muscle, and liver by physiological (fasting), pathophysiological (insulin deficiency), pharmacological (peroxisome proliferator-activated receptor [PPAR] agonists), and genetic (muscle-specific PPARalpha overexpression) perturbations that increase fatty acid utilization. In humans with impaired glucose tolerance, PPARgamma agonist treatment induces adipose OXPAT mRNA. Further, adipose OXPAT mRNA negatively correlates with BMI in nondiabetic humans. Our collective data in cells, mice, and humans suggest that OXPAT is a marker for PPAR activation and fatty acid oxidation. OXPAT likely contributes to adaptive responses to the fatty acid burden that accompanies fasting, insulin deficiency, and overnutrition, responses that are defective in obesity and type 2 diabetes.
PAT（围脂滴蛋白、脂肪亲和素和TIP47）家族的脂滴蛋白调节细胞内中性脂质储存。我们研究了该家族的一个新成员PAT-1，发现它在高氧化组织中表达。我们将这种蛋白质称为“OXPAT”。通过禁食使小鼠肝脏进行生理性脂质加载，可使脂质滴组织部分中的OXPAT富集。在原代心肌细胞中，OXPAT与PAT蛋白脂肪亲和素一起存在于脂质滴上。OXPAT的异位表达促进脂肪酸诱导的三酰甘油积累、长链脂肪酸氧化以及与氧化代谢相关的mRNA表达。与这些观察结果一致，在生理（禁食）、病理生理（胰岛素缺乏）、药理（过氧化物酶体增殖物激活受体[PPAR]激动剂）和遗传（肌肉特异性PPARα过表达）等增加脂肪酸利用的扰动情况下，小鼠脂肪组织、横纹肌和肝脏中会诱导OXPAT表达。在糖耐量受损的人类中，PPARγ激动剂治疗可诱导脂肪组织中OXPAT mRNA表达。此外，在非糖尿病人类中，脂肪组织OXPAT mRNA与BMI呈负相关。我们在细胞、小鼠和人类中的综合数据表明，OXPAT是PPAR激活和脂肪酸氧化的标志物。OXPAT可能有助于对伴随禁食、胰岛素缺乏和营养过剩的脂肪酸负担产生适应性反应，而肥胖和2型糖尿病患者的这些反应存在缺陷。
