Evidence for protein-mediated fatty acid efflux by adipocytes.
Evidence for protein-mediated fatty acid efflux by adipocytes.
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DOI：
10.1111/j.1748-1716.2011.02367.x
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Stahl A
中科院分区：
文献类型：
--
作者：
Henkin AH;Ortegon AM;Cho S;Shen WJ;Falcon A;Kraemer FB;Lee SJ;Stahl A
脂肪酸从脂肪细胞向循环中的经尿道控制的动员和释放是能量稳态所需的重要生理过程。虽然脂肪细胞对脂肪酸的摄取被认为主要是蛋白质介导的，但尚不清楚脂肪酸的流出是否也需要膜蛋白。我们使用荧光脂肪酸流出测定和游离脂肪酸和甘油的比色测定来鉴定3 T3-L1脂肪细胞中对脂肪酸流出有影响但对脂解无影响的抑制剂。我们评估了这些抑制剂对表达脂肪酸转运蛋白1、脂肪酸敏感脂肪酶和脂周蛋白的成纤维细胞系的影响，这些细胞系可能缺乏脂肪酸流出的脂肪细胞特异性蛋白。我们确定DIDS作为脂肪酸流出的抑制剂，不损害脂解或甘油的细胞出口，但导致细胞内脂肪酸的积累。相反，脂肪酸流出的重建细胞模型的脂肪酸流出是响应脂解刺激，但不敏感的DIDS抑制。我们提出，脂肪细胞特异性表达一种尚未鉴定的DIDS敏感蛋白，该蛋白增强脂肪酸的流出，因此可能导致以异常脂质通量和异位甘油三酯积聚为特征的肥胖相关疾病的新治疗方法。
The hormonally controlled mobilization and release of fatty acids from adipocytes into the circulation is an important physiological process required for energy homeostasis. While uptake of fatty acids by adipocytes has been suggested to be predominantly protein-mediated, it is unclear whether the efflux of fatty acids also requires membrane proteins. We used fluorescent fatty acid efflux assays and colorimetric assays for free fatty acids and glycerol to identify inhibitors with effects on fatty acid efflux, but not lipolysis, in 3T3-L1 adipocytes. We assessed the effect of these inhibitors on a fibroblast-based cell line expressing fatty acid transport protein 1, hormone-sensitive lipase, and perilipin, that presumably lacks adipocyte-speicific proteins for fatty acid efflux. We identified DIDS as an inhibitor of fatty acid efflux that did not impair lipolysis or the cellular exit of glycerol, but lead to an accumulation of intracellular fatty acids. In contrast, fatty acid efflux by the reconstituted cellular model for fatty acid efflux was responsive to lipolytic stimuli, but insensitive to DIDS inhibition. We propose that adipocytes specifically express an as yet unidentified DIDS sensitive protein that enhances the efflux of fatty acids and therefore may lead to novel treatment approaches for obesity-related disorders characterized by abnormal lipid fluxes and ectopic triglyceride accumulation.
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DOI：
10.1073/pnas.89.11.5049
发表时间：
1992-06-01
影响因子：
11.1
作者：
BALDINI, G;HOHL, T;LODISH, HF
通讯作者：
LODISH, HF
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
DOI：
10.1046/j.1365-201x.2003.01157.x
发表时间：
2003-08-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Bonen, A;Benton, CR;Luiken, JJFP
通讯作者：
Luiken, JJFP
DOI：
10.1097/00075197-200203000-00004
发表时间：
2002-03-01
影响因子：
3.1
作者：
Ibrahimi, A;Abumrad, NA
通讯作者：
Abumrad, NA
影响因子：
7.7
作者：
Cohen, AW;Schubert, W;Lisanti, MP
通讯作者：
Lisanti, MP