CLA Reduces Adipogenesis In Human Preadipocytes

描述（从申请人的描述中扫描）：膳食脂质 会导致大量的能量摄入，从而导致 肥胖及相关疾病的发展。然而，某些脂肪， 适量食用有益健康。例如，动物和细胞培养 研究表明，抗肿瘤、抗动脉粥样硬化， 共轭的异构体的粗混合物的降胆固醇性质 亚油酸（CLA），一种存在于牛肉和奶制品中的不饱和脂肪酸。 此外，小鼠和猪喂食低水平的商业制备的 CLA异构体（例如，大约40%的顺式-9，反式-11和40%的 反式-10，顺式-12共轭亚油酸）比对照组具有更少的体脂肪。这些研究 表明在动物饮食中添加CLA可能有助于预防或 减缓肥胖症和相关疾病的发展。然而， CLA对人体脂肪的影响是相互矛盾的。我们认为这种差异的一部分 可能是由于在这些研究中使用的CLA异构体的类型和数量。在 为了支持这一观点，我们最近证明了反式-10，顺式-12， 而CLA的顺式-9、反式-11异构体则不降低TG含量， 小鼠3 T3-L1和人前脂肪细胞的分化培养物。这些数据 提示CLA异构体立体特异性和可能的调节作用， 脂肪生成然而，CLA改变细胞分化的机制 前脂肪细胞的情况尚不清楚。此外，尽管CLA明显减弱了身体 脂肪在动物中，潜在的抗肥胖特性的共轭亚油酸在人类中是 有争议，需要进一步检查。我们假设CLA抑制了 脂肪形成通过减少细胞水平的花生四烯酸（AA）， 其代谢物激活过氧化物酶体增殖物的不饱和脂肪酸 活化受体γ（PPAR-gamma）和前脂肪细胞分化。在 为了验证这一假设，需要NIH区域基金的支持， 在人前脂肪细胞的原代培养物中检查：1）CLA是否减弱 通过抑制脂肪生成、增强脂肪分解或 降低脂质激活转录因子PPAR-gamma的激活 控制脂肪生成; 2）如果CLA与亚油酸竞争， 掺入细胞AA，前列腺素类的前体，调节 脂肪细胞分化从这项研究中获得的数据预计将 扩大我们对CLA特定异构体如何影响人类脂肪的了解 组织质量和肥胖的发展，并导致提交一个 未来的NIH R 01资助。

DESCRIPTION (Scanned from the Applicant's Description): Dietary lipids contribute significantly to excess energy intake, which leads to the development of obesity and related diseases. However, certain fats when consumed in moderation promote health. For example, animal and cell culture studies have demonstrated antitumorigenic, antiatherogenic, and hypocholesterolemic properties of a crude mixture of isomers of conjugated linoleic acid (CLA), an unsaturated fatty acid found in beef and dairy foods. Furthermore, mice and pigs fed low levels of a commercially prepared mixture of CLA isomers (e.g., approximately 40 percent cis-9, trans-11 and 40 percent trans-10, cis-12 CLA) had less body fat than the controls. These studies suggest that the inclusion of CLA in the diet of animals may help prevent or attenuate the development of obesity and related diseases. However, effects of CLA on human body fat are conflicting. We believe that part of this discrepancy may be due to the type and amount of CLA isomers used in these studies. In support of this idea, we have recently demonstrated that the trans-10, cis-12, but not the cis-9, trans-11, isomer of CLA decreased the TG content of differentiating cultures of murine 3T3-L1 and human preadipocytes. These data suggest stereospecificity of CLA isomers and a possible regulatory role in adipogenesis. However, the mechanism(s) by which CLA alters the differentiation of preadipocytes is unclear. Furthermore, whereas CLA clearly attenuates body fat in animals, potential antiobesity properties of CLA in humans are disputable and require further examination. We hypothesize that CLA suppresses adipogenesis by reducing cellular levels of arachidonic acid (AA), an unsaturated fatty acid whose metabolites activate peroxisome proliferator activated receptor gamma (PPAR-gamma) and preadipocyte differentiation. In order to test this hypothesis, support is requested from this NIH AREA grant to examine in primary cultures of human preadipocytes: 1) whether CLA attenuates TG content by either suppressing lipogenesis, enhancing lipolysis, or decreasing the activation of PPAR-gamma, a lipid-activated transcription factor that controls adipogenesis; and 2) if CLA competes with linoleic acid for incorporation into cellular AA, a precursor of prostanoids that regulate adipocyte differentiation. Data obtained from this research are expected to expand our knowledge of how specific isomers of CLA influence human adipose tissue mass and the development of obesity and lead to the submission of a future NIH R01 grant.