Investigation of the Effects of Β-2 Stimulation on Free Fatty Acids in Man

Abstract

In this study we present evidence that lipolysis in man is under beta-2 adrenergic control and that beta-2 stimulation produces a characteristic profile of individual free fatty acid (FFA) release. Twelve healthy volunteers received infusions of placebo (N Saline), terbutaline (a selective beta-2 agonist) and dilevalol (a new non-selective beta-blocker with beta-2 agonist activity). Plasma FFA concentrations during and after the infusions were measured using gas chromatography. A significant rise in total and individual FFAs was seen after 30 min of terbutaline infusion. This was most marked for oleic acid. Total and individual FFA concentrations also rose after 30 min of dilevalol infusion; this was only significant for oleic acid and was approximately 15% of the rise induced by terbutaline infusion. Placebo infusion did not cause any significant changes in FFA levels.

Impact of salbutamol on muscle metabolism assessed by 31P NMR spectroscopy

“…Several studies also mentioned that salbutamol may induce a significant increase in blood glucose concentrations and may possibly modify carbohydrates availability and utilization (Collomp et al., 2000a,b; Le Panse et al., ; Sanchez et al., ). It has been shown that β2‐agonists can induce a stimulation of hepatic glucose production and glucose release (Clutter et al., ), a stimulation of glycogenolysis and glycolysis with increased lactate and pyruvate release from tissues such as muscle (Rizza et al., ), a stimulation of lipolysis with increased glycerol and fatty acid release and lipid oxidation (Kendall et al., ; Schiffelers et al., ). Some studies reported no significant difference in total energy expenditure and substrate oxidation (based on gas exchange measurement during whole‐body exercise) following salbutamol administration, but the substrate oxidation balance might be modified during and after exercise (Collomp et al., 2000a,b, 2005; Arlettaz et al., ).…”

“…Several studies also mentioned that salbutamol may induce a significant increase in blood glucose concentrations and may possibly modify carbohydrates availability and utilization (Collomp et al, 2000a,b;Le Panse et al, 2007;Sanchez et al, 2012). It has been shown that β2-agonists can induce a stimulation of hepatic glucose production and glucose release (Clutter et al, 1980), a stimulation of glycogenolysis and glycolysis with increased lactate and pyruvate release from tissues such as muscle (Rizza et al, 1980), a stimulation of lipolysis with increased glycerol and fatty acid release and lipid oxidation (Kendall et al, 1991;Schiffelers et al, 1999).…”

Selective versus nonselective β‐adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization

“…These important differences between carvedilol and metoprolol could have resulted from differential effects of these agents on peripheral lipolysis. The non‐selective β‐adrenergic receptor blocking activity of carvedilol might provide a more complete suppression of lipolysis given its ability to block both β 1 ‐ and β 2 ‐receptors [18,22,23]. The associated reduction in serum FFA could lower cardiac extraction of FFA since the uptake of FFA has been shown to be concentration dependent [24].…”

“…Investigations in animal models of CHF suggest that β‐blockers may reduce myocardial utilization of free fatty acids. In humans with CHF, information concerning the impact of β‐blockers on energy substrate utilization and efficiency remains limited and, to some extent, contradictory [16–18]. To date, no studies have compared the impact of different β‐blockers on these parameters in patients with CHF.…”

Assessment of Β-1 Selectivity of Bisoprolol and Atenolol by Means of Their Influence on the Lipolytic Response to an Infusion of Terbutaline

“…None of the mean changes in FFA concentration at 60 rnin were statistically significant but all were less than the values at 30 min. We and many others have shown previously that infusion of a 8-2 receptor agonist into human volunteers causes a rise in plasma FFA concentration (10,14,15). Terbutaline is a p-2 specific agent and attenuation of its effect on lipolysis by another agent thus indicates p-2 blocking activity.…”