Beta-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 beta-adrenergic pathway. Rats were kept at 24 degreesC or exposed to 10 degreesC for 3 h after acute administration of the beta-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 degreesC, 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 (approximately 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 beta-adrenergic pathway.