Direct regulation of ion channels by fatty acids

Ordway, Richard W.; Singer, Joshua J.; Walsh, John V.

doi:10.1016/0166-2236(91)90069-7

Cited by 370 publications

(191 citation statements)

References 45 publications

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“…FFAs act as potent activators of phosphorylation of protein kinase C. 17 Other studies have reported a direct action of FFAs released from phospholipids on ion channels at the cellular membranes of smooth muscle cells and other tissues. 18 Hall et al 19 have reported that plasma renin activity displays a significant increase during obesity, despite extracellular-fluid volume expansion and sodium retention in dogs fed with a high-fat diet. Moreover, studies in patients under sodium restriction, which activates the rennin-Ang system (RAS), provided evidence for a presynaptic potentiating effect of Ang II on sympathetic neurotransmission.…”

Section: Sympathetic Activation In Obesitymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. Hypertension Research (2010) 33, 386-393; doi:10.1038/hr.2010.9Keywords: leptin; obesity; pressure natriuresis; rennin-angiotensin-aldosterone system; sympathetic nervous system INTRODUCTION Obesity is a common disorder that develops from the interaction between the genotype and the environment and involves social, behavioral, cultural, physiological, metabolic and genetic factors. A large number of studies have shown that obesity has an important negative impact on health in a population, leading to the recommendation for general practitioners to have an important function in the management of this condition and of its associated comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia/insulin resistance. The relationship between obesity and hypertension is well established both in adults and children. 1,2 Obese individuals exhibit higher levels of office as well as ambulatory blood pressure (BP) from childhood to old age. Obese subjects display higher BP levels than non-obese individuals even in the normotensive range. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the probability of adverse cardiovascular outcomes, and raises considerations for aggressive treatment strategies. 3 The mechanisms through which obesity directly causes hypertension are still an area of research. Human and animal studies have elucidated the function of adipose tissue derivatives (adipokines and cytokines), neurohumoral pathways, metabolic functions and modulation of pressor/depressor mechanisms. Although obesity-related hypertension may be the result of a combinatio...

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Section: Sympathetic Activation In Obesitymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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“…FA can affect the plasma membrane ionic channels in a direct or indirect way (Ordway et al, 1991). The indirect effects of these compounds are mediated by the products of its metabolism, specially by the ones that can be oxygenated through cyclooxygenase, lipooxygenase, and P-450 cytochrome oxidation ways, as AA (Needleman et al, 1986).…”

Section: Effect Of Ffa On Ionic Channelsmentioning

confidence: 99%

“…An important property of this effect is the structural feature of FA (Ordway et al, 1991). The medium-chain FA (MCFA) are more potent than the shorter-or long-chain FA.…”

Section: Effect Of Ffa On Ionic Channelsmentioning

confidence: 99%

Pleiotropic effects of fatty acids on pancreatic β‐cells

Haber

Ximenes

Procópio

et al. 2002

Journal Cellular Physiology

148

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Hyperlipidemia is frequently associated with insulin resistance states as found in type 2 diabetes and obesity. Effects of free fatty acids (FFA) on pancreatic b-cells have long been recognized. Acute exposure of the pancreatic b-cell to FFA results in an increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. We recently showed that palmitate augments insulin release in the presence of non-stimulatory concentrations of glucose. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release. These results imply that physiological plasma levels of FFA are important for b-cell function. Although, it has been accepted that fatty acid oxidation is necessary for its stimulation of insulin secretion, the possible mechanisms by which fatty acids (FA) affect insulin secretion are discussed in this review. Long-chain acylCoA (LC-CoA) controls several aspects of the b-cell function including activation of certain types of protein kinase C (PKC), modulation of ion channels, protein acylation, ceramide-and/or nitric oxide (NO)-mediated apoptosis, and binding to nuclear transcriptional factors. The present review also describes the possible effects of FA on insulin signaling. We showed for the first time that acute exposure of islets to palmitate upregulates the intracellular insulin-signaling pathway in pancreatic islets. Another aspect considered in this review is the source of FA for pancreatic islets. In addition to be exported to the medium, lipids can be transferred from leukocytes (macrophages) to pancreatic islets in co-culture. This process consists an additional source of FA that may plays a significant role to regulate insulin secretion.

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“…Several ion channels of the plasma membrane have been shown to be influenced by AA [20][21][22]. In most cases AA itself seems to be the effective agent, but the cardiac K+-channel was only stimulated by leukotrienes and other derivatives produced on the lipoxygenase pathway [22].…”

Section: Is Aa Itself or One Of Its Metabolites The Effective Agent?mentioning

confidence: 99%