β-Adrenergic modulation of triglyceridemia under increased energy expenditure

Abstract

This study aimed to identify the metabolic steps involved in the acute hypotriglyceridemia brought about by increased energy expenditure (cold exposure) and to assess the causative involvement of some determinants of triglyceride (TG) metabolism as well as that of the β-adrenergic pathway. Rats were kept at 24°C or exposed to 10°C for 3 h after acute administration of the β-adrenergic antagonist propranolol (Prop) or vehicle. Cold exposure increased the rate of TG secretion (Triton WR1339 method) into the circulation by 50% ( P < 0.0005), an effect that was blunted by Prop. The cold-induced increase in TG secretion was closely related to changes in circulating nonesterified fatty acid levels, but not with serum insulin concentrations. Despite an increase in TG secretion, serum TG levels after acute cold exposure fell to 50% ( P < 0.002) of those measured at 24°C, indicating that the lowering of serum TG was entirely due to an increase in their rate of intravascular hydrolysis. This was confirmed by observing a 70% increase ( P < 0.002) in the rate of clearance of an exogenous TG emulsion in cold-exposed rats compared with those kept in the warm. Prop treatment before cold exposure decreased (∼30%, P < 0.005) the cold-induced stimulation of TG hydrolysis. The increased TG clearance rate in cold-exposed animals occurred in the absence of any change in the intravascular availability of lipoprotein lipase (LPL). In contrast, the activity of LPL displayed a tissue-specific response to cold exposure, being reduced by one-half in white adipose tissue ( P < 0.0005) and increased in brown adipose tissue (130%, P < 0.0001) and the heart (50%, P < 0.001). These findings show that, in the postprandial state, an acute increase in energy expenditure induced by cold exposure results in a lowering of serum TG entirely due to an increase in their rate of intravascular hydrolysis and that serum TGs are lowered despite an increase in the rate of TG secretion into the circulation. More efficient TG hydrolysis occurs independently of the intravascular availability of LPL. The study further shows that the effects of cold exposure on serum TG concentration and their rates of secretion and clearance are in large part mediated by the β-adrenergic pathway.

Cold Exposure Partially Corrects Disturbances in Lipid Metabolism in a Male Mouse Model of Glucocorticoid Excess

“…Cold exposure increases BAT activity and hence the uptake of VLDL-TGderived FA by this tissue (11,12), thus one might expect the body to compensate for this by enhancing the hepatic VLDL-TG secretion. In rats, 3 hours of exposure to 10°C increased VLDL secretion and this effect of cold could be prevented by administration of the nonspecific ␤-adrenergic antagonist propranolol (38). The latter finding is in sharp contrast to what we find.…”

Abnormal insulin and ?-adrenergic modulation of lipoprotein lipase during refeeding after prolonged fasting in the Zucker rat

“…Hence the selection of the nonspecific b-adrenergic antagonist propranolol, which is able to antagonise actions mediated by b1, b2, as well as b3 [29,30]. Propranolol at the dose used here has been shown to prevent in vivo the exercise-induced increase in plasma NEFA [31] and to antagonise the alterations in tissue LPL brought by short-term cold exposure [32].…”

Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis

“…21,77 It is possible that acute cold exposure causes a rapid increase in hepatic VLDL-triglyceride production that can mask a potential BAT-mediated decrease in plasma triglyceride. Indeed, acute cold activation increases hepatic VLDL-triglyceride secretion in rats 78 and possibly also in humans (G. Hoeke, MSc, et al, unpublished data, 2015).…”

“…89 Although not yet demonstrated in Ldlr −/− and Apoe −/− mice, cold exposure indeed increases hepatic VLDL production in rats. 78 Thus, the available data suggest that an intact apoE-LDLR pathway is crucial for the cholesterol-lowering effect of BAT activation and show that BAT activation in mice might be a potent tool to combat hypercholesterolemia and atherosclerosis development. However, in line with the data of Dong et al, 89 when activated by cold, the beneficial effects of BAT activation on plasma cholesterol levels may be dampened because of a concomitant increase in hepatic cholesterol synthesis.…”