Regulatory Actions of Fatty Acids in Rat Adrenal Cortex

9513926 Widmaier脂肪酸在生物体中具有多种功能。这些脂质是细胞膜的组成部分，是身体大多数细胞的重要燃料来源。此外，脂肪酸似乎在细胞与细胞之间的通讯中起着重要作用。换句话说，脂肪酸可能在体内具有“调节”作用，介导激素和神经信号。某些脂肪酸在这方面比其他脂肪酸更有效。长链不饱和硬脂酸酯的活性最低。当血液中的油酸水平高时，几种内分泌腺的功能受到影响，通常是以负面的方式（即，抑制）。脂肪酸引起细胞功能变化的一个很好的模型是肾上腺，特别是产生糖皮质激素的类固醇激素（人的皮质醇，大鼠的皮质酮）的腺体区域（皮质）。在这项资助中，将通过多种方法研究特定脂肪酸诱导肾上腺活性变化的机制。这些研究包括将脂肪酸注入大鼠体内，然后分析激素分泌，以及培养的肾上腺细胞对添加各种脂肪酸的反应。这些实验的结果将大大增加我们对类固醇生成腺如肾上腺（和性腺）在正常和高脂肪条件下如何调节的理解。此外，还将获得与脂肪酸相关的细胞信号事件的基本信息。这一点很重要，因为对脂肪酸敏感的组织阵列是巨大的，包括胰腺，卵巢，睾丸，垂体，肝脏，心脏，肌肉等。从这些研究中获得的信息可能有助于神经生物学家了解脂肪酸如何诱导肌肉膜对电解质的渗透性变化，分子生物学家了解脂肪酸如何有助于调节胰岛素分泌。人们对这些脂质广泛而有力的调节作用的认识正在迅速增长。这笔赠款将开始系统地探索产生这些行动的机制。

9513926 Widmaier Fatty acids serve numerous functions in living organisms. These lipids are building-blocks of cell membranes, and are a vital fuel source for most cells of the body. In addition, fatty acids appear to play an important role in cell:cell communication. In other words, fatty acids may have "regulatory" actions in the body that mediate hormonal and nervous signals. Certain fatty acids are more potent in this regard than others. The long-chain, unsaturated stearate are the least active. When blood levels of oleate are high, the function of several endocrine glands is affected, usually in a negative way (i.e., inhibited). One good model of fatty acid-induced changes in cell function is the adrenal gland, specifically the region of the gland (the cortex) that produces the steroid hormones known as glucocorticoids (cortisol in people, corticosterone in rats). In this grant, the mechanisms by which specific fatty acids induce changes in adrenal activity will be investigated by a variety of approaches. These include infusions of fatty acids into rats followed by analysis of hormone secretion, and the responses of cultured adrenal cells to additions of various fatty acids. The results of these experiments will significantly increase our understanding of how steroidogenic glands like the adrenal glands (and the gonads) are regulated under normal and high-fat conditions. In addition, basic information about cell signaling events associated with fatty acids will be obtained. This is important because the array of tissues that are sensitive to fatty acids is enormous, including the pancreas, ovary, testis, pituitary, liver, heart, muscle and others. Information gained from these studies may be expected to help neurobiologists understand how fatty acids induce changes in muscle membrane permeability to electrolytes, molecular biologists understand how fatty acids contribute to regulation of insulin secretion. An appreciation of the widespread and potent regulatory action s of these lipids is rapidly growing. This grant will begin the systematic exploration of the mechanisms by which these actions are produced.