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.
