Brown N F, Hill J K, Esser V, Kirkland J L, Corkey B E, Foster D W, McGarry J D
Department of Internal Medicine, Gifford Laboratories, Center for Diabetes Research, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75235-9135, USA.
Biochem J. 1997 Oct 1;327 ( Pt 1)(Pt 1):225-31. doi: 10.1042/bj3270225.
The outer mitochondrial membrane enzyme carnitine palmitoyltransferase I (CPT I) represents the initial and regulated step in the beta-oxidation of fatty acids. It exists in at least two isoforms, denoted L (liver) and M (muscle) types, with very different kinetic properties and sensitivities to malonyl-CoA. Here we have examined the relative expression of the CPT I isoforms in two different models of adipocyte differentiation and in a number of rat tissues. Adipocytes from mice, hamsters and humans were also evaluated. Primary monolayer cultures of undifferentiated rat preadipocytes expressed solely L-CPT I, but significant levels of M-CPT I emerged after only 3 days of differentiation in vitro; in the mature cell M-CPT I predominated. In sharp contrast, the murine 3T3-L1 preadipocyte expressed essentially exclusively L-CPT I, both in the undifferentiated state and throughout the differentiation process in vitro. This was also true of the mature mouse white fat cell. Fully developed adipocytes from the hamster and human behaved similarly to those of the rat. Thus the mouse white fat cell differs fundamentally from those of the other species examined in terms of tis choice of a key regulatory enzyme in fatty acid metabolism. In contrast, brown adipose tissue from all three rodents displayed the same isoform profiles, each expressing overwhelmingly M-CPT I. Northern blot analysis of other rat tissues established L-CPT I as the dominant isoform not only in liver but also in kidney, lung, ovary, spleen, brain, intestine and pancreatic islets. In addition to its primacy in skeletal muscle, heart and fat, M-CPT I was also found to dominate the testis. The same inter-tissue isoform pattern (with the exception of white fat) was found in the mouse. Taken together, the data bring to light an intriguing divergence between white adipocytes of the mouse and other mammalian species. They also raise a cautionary note that should be considered in the choice of animal model used in further studies of fat cell physiology.
线粒体外膜酶肉碱棕榈酰转移酶I（CPT I）是脂肪酸β氧化的起始步骤且受其调控。它至少存在两种同工型，分别称为L（肝脏）型和M（肌肉）型，二者的动力学特性以及对丙二酰辅酶A的敏感性差异很大。在此，我们研究了CPT I同工型在两种不同的脂肪细胞分化模型以及多种大鼠组织中的相对表达情况。我们还对来自小鼠、仓鼠和人类的脂肪细胞进行了评估。未分化的大鼠前脂肪细胞的原代单层培养物仅表达L-CPT I，但在体外分化仅3天后就出现了显著水平的M-CPT I；在成熟细胞中，M-CPT I占主导地位。与之形成鲜明对比的是，小鼠3T3-L1前脂肪细胞在未分化状态以及体外整个分化过程中基本上只表达L-CPT I。成熟的小鼠白色脂肪细胞也是如此。来自仓鼠和人类的完全发育的脂肪细胞表现与大鼠的相似。因此，就脂肪酸代谢关键调节酶的选择而言，小鼠白色脂肪细胞与其他所研究物种的脂肪细胞存在根本差异。相比之下，所有三种啮齿动物的棕色脂肪组织呈现相同的同工型谱，均以表达M-CPT I为主。对其他大鼠组织的Northern印迹分析表明，L-CPT I不仅在肝脏中是主要同工型，在肾脏、肺、卵巢、脾脏、大脑、肠道和胰岛中也是如此。除了在骨骼肌、心脏和脂肪中占主导地位外，M-CPT I在睾丸中也占主导。在小鼠中也发现了相同的组织间同工型模式（白色脂肪除外）。综上所述，这些数据揭示了小鼠白色脂肪细胞与其他哺乳动物物种之间有趣的差异。它们还提出了一个警示，在进一步研究脂肪细胞生理学所使用的动物模型选择中应予以考虑。
