Cardiovascular and Metabolic Research, Johnson and Johnson Pharmaceutical Research and Development, Welsh and McKean Roads, Springhouse, PA 19477, USA.
Curr Pharm Des. 2011;17(4):325-31. doi: 10.2174/138161211795164185.
Since storage of excess fat in peripheral tissues is a contributing factor leading to obesity and type II diabetes, many investigators are studying the key lipid metabolizing enzymes found in adipose tissue as drug targets to reduce excess fat. The availability of cultured cell lines and primary stem cells, preadipocyetes, and adipocytes has facilitated therapeutic approaches aimed at targeting fat storage. This includes developing inhibitors for enzymes regulating lipogenesis in these cells, such as acetyl-CoA carboxylase, fatty acid synthase, diacylgycerol acyl transferase, and stearoyl CoA desaturase. High level expression of each protein is often used to confirm stem cells have undergone adipogenesis. Inhibition of these enzymes often leads to reduced fat cell fat differentiation and lipid synthesis and may also contribute to increased fat oxidation and energy expenditure. This article reviews developments in pharmaceutical research on these enzymes, with particular emphasis on the role of the enzymes in adipose tissue metabolism.
由于外周组织中多余脂肪的储存是导致肥胖和 II 型糖尿病的一个因素，许多研究人员正在研究脂肪组织中发现的关键脂质代谢酶，将其作为药物靶点来减少多余脂肪。培养的细胞系和原代干细胞、前脂肪细胞和脂肪细胞的可用性促进了针对脂肪储存的治疗方法。这包括开发针对这些细胞中调节脂肪生成的酶的抑制剂，如乙酰辅酶 A 羧化酶、脂肪酸合酶、二酰基甘油酰基转移酶和硬脂酰辅酶 A 去饱和酶。每种蛋白质的高水平表达通常用于确认干细胞已经经历了脂肪生成。这些酶的抑制通常会导致脂肪细胞脂肪分化和脂质合成减少，并且还可能导致脂肪氧化和能量消耗增加。本文综述了这些酶在药物研究方面的进展，特别强调了这些酶在脂肪组织代谢中的作用。
