Free Fatty Acid Mobilization by Neuroadrenergic Stimulation in Man*

Abstract

A role of the sympathetic nervous system in the metabolism of adipose tissue has been suggested by clinical observations and by animal denervation experiments (1). The recent observations of the mobilization of free fatty acids' (FFA) by norepinephrine (NE) in vitro (2) and in vivo (3, 4) add presumptive evidence for a function of the sympathetic nervous system in the transport of fatty acids. To elucidate further the role of the sympathetic nervous system in fatty acid transport, the effect of a standard physiological stress on plasma FFA concentration was studied.Previous work has shown that the normal individual defends against the orthostatic stress of a 60°upright tilt by an increase in diastolic blood pressure and pulse rate. This response is probably mediated by the autonomic nervous system through baroceptor reflexes and is accompanied by a rise in plasma NE concentration (5). These responses reflect an increase in neuroadrenergic activity; and, as a corollary, are absent in individuals after sympathectomy and in patients with primary autonomic insufficiency.It is the purpose of this report to present the effects of neuroadrenergic stimulation produced by orthostatic stress on plasma FFA concentration. METHODSThe response of plasma FFA and NE to tilting was studied in 6 normal subjects, in 1 patient with bilateral adrenalectomy, and in 1 patient with primary autonomic t Public Health Service Postdoctoral Fellow, National Heart Institute, Bethesda, Md.1 The term "free fatty acids" is used here in place of the terms "nonesterified fatty acids" and "unesterified fatty acids" previously used to describe this lipid fraction.insufficiency. All studies were carried out with fasting subjects in the supine position on a tilt table. An indwelling needle was secured in an antecubital vein and was kept patent for the collection of blood specimens by a slow infusion of sterile isotonic saline. Pulse rate and blood pressure were recorded until a steady state was achieved. The subject was then tilted 600 upright for 30 minutes. Pulse and blood pressure were recorded at regular intervals throughout the experiment. Blood specimens for plasma FFA and NE were drawn 10 minutes before and immediately prior to tilting to 600 upright and at 2.5, 5, 10, 20 and 30 minutes in the upright position. The subject was then returned to the supine position and another blood specimen was drawn 10 minutes later.The effect of an adrenolytic agent, phentolamine methanesulfonate,2 on the plasma FFA response to tilting was studied in 3 normal individuals. Each subj ect served as his own control. The FFA and NE responses were determined during a 30 minute control tilt after which 5 mg of phentolamine was administered intravenously and the subj ect was tilted a second time. One subj ect was studied again 1 month later with a dose of 10 mg of phentolamine.The effect of 2 successive tilts was studied in 3 normal subjects without administering phentolamine prior to the second tilt.All blood specimens were collected in tubes with phenol-free hepari...

Some Problems Arising from Post-Operative Utilisation of Fat

“…It is possible that the psychic stimuli normally act through the adrenal medulla but the adrenal glands are not absolutely necessary for the effect on plasma NEFA. Plasma NEFA levels can be increased after bilateral adrenalectomy by neuroadrenergic stimulation of a kind inhibited by phentolamine (Hamlin, Hickler and Hoskins, 1960) and this evidence supports the concept that the autonomic nervous system plays a significant role in the mobilisation of NEFA in man.…”

Free Fatty Acids, Central Nervous System and Bromazepam

“…A lot of research work, during the last years, refers to the CNS infiuence on the mobilization of free fatty acids (l - 5,9). The exact mechanism of such an infiuence is still unsettled, since the clinical studies äs well äs the experimcntal ones have lead to various hypotheses äs to the direct or indirect infiuence of the CNS on lipid metabolism.…”

“…Similar studies, clinical or experimentaJ, show that any CNS Stimulation, physical (9, 10, 13) or psychological (1,4,14), results in plasma free fatty acid elevation. On the other band, peripheral blockade of the syrnpathetic "autonomic" nervous System by means of adrenergie or ganglionic blocking agents, inhibits the Physiologie response of increased free fatty acids after threatening Stimuli (5,(15)(16)(17)(18). Experimental studies on animals pr ve the necessity of the peripheral nerve integrity in order to maintain an equilibrium in lipid metabolism (19).…”

“…The concentration of free fatty acids in plasma is generally accepted äs a sensitive measure of CNS arousal (1)(2)(3)(4)(5)(6).…”

Free Fatty Acid Metabolism during Perinatal Life

“…In m an , p sy ch ic stim u li such as p a in or a n x ie ty will cause an elev atio n of p lasm a F F A [6]. T he release o f F F A from adipose tissu e is v ery se n sitiv e to m in u te a m o u n ts o f n o rep in ep h rin e in th e circu latio n , as w ell as t h a t lib e ra te d from stim u la tio n of sy m p a th e tic n erves in ad ip o se tissu e. On th e o th e r h a n d , depression o f n ervous sy stem a c tiv ity b y sed atio n or gen eral a n e sth esia will depress F F A levels [5 ,6 ].…”