Fatty Acid Regulation of Endocrine Activity

  • Eric P. Widmaier


The effects of nonesterified fatty acids (NEFA) on endocrine activity are widespread and found in virtually every animal species in which it has been examined. The most potent lipids are generally long-chain unsaturated fats like oleic, linoleic, and arachidonic acids. Not surprisingly, many of the hormones whose secretion and synthesis is under fatty acid (FA) control have potent metabolic actions. For example, NEFA modulate secretion of insulin (hypoglycemic hormone), growth hormone (GH) (hyperglycemic and hyperlipidemic), and glucocorticoids (GC) (hyperglycemic and hyperlipidemic), as well as the hypothalamic-releasing hormones that mediate GH and GC secretion. In most cases, NEFA are inhibitory in endocrine cells, and attenuate secretion of GH, aldosterone, insulin (only with chronic exposure), and somatostatin. On the other hand, NEFA stimulate growth hormone-releasing hormone (GHRH), GC production, and (acutely) insulin release. The mechanisms by which NEFA exert these actions are varied. These lipids inhibit binding of certain hormones like angiotensin II (ATI) to membrane receptors on target cells, and also act intracellularly on these and perhaps other endocrine cells to modulate enzyme activity. NEFA also alter binding of lipophilic hormones to intracellular steroid hormone receptors. Moreover, NEFA may modulate binding of lipophilic hormones to their plasma-binding globulins, thus influencing the ratio of bound/free hormone and changing the amount of “active” (free) hormone available for uptake by cells. In some cases, the effects of NEFA on endocrine cells require intracellular oxidation, suggesting that the actions of the lipids on such cells is indirect and mediated by some intracellular product of FA metabolism. The physiological significance of these actions remains to be fully elucidated. Nonetheless, it is clear that the inhibitory influence of NEFA on lipolytic hormones like GH is part of an intricate feedback loop that contributes to metabolic homeostasis. The actions of NEFA on other hormones, like aldosterone, may be more relevant to pathophysiology, for example in obesity, starvation, critical illness, or diabetes, when circulating levels of NEFAs are elevated and may contribute to some of the symptoms of these disorders.


Growth Hormone Free Fatty Acid Oleic Acid Endocrine Cell Endocrine Activity 
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  • Eric P. Widmaier

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