Glycerokinase activity in brown adipose tissue: a sympathetic regulation?

Abstract

The effect of brown adipose tissue (BAT) sympathetic hemidenervation on the activity of glycerokinase (GyK) was investigated in different physiological conditions. In rats fed a balanced diet, the activity of the enzyme was ∼50% lower in BAT-denervated pads than in intact, innervated pads. In rats adapted to a high-protein, carbohydrate-free diet, norepinephrine turnover rates and BAT GyK activity were already reduced, and BAT denervation resulted in a further decrease in the activity of the enzyme. Cold acclimation of normally fed rats at 4°C for 10 days markedly increased the activity of the enzyme. Cold exposure (4°C) for 6 h was insufficient to stimulate BAT GyK, but the activity of the enzyme was already increased after 12 h of cold exposure. The cold-induced BAT GyK stimulation was completely blocked in BAT-denervated pads. The data indicate that an adequate sympathetic flow to BAT is required for the maintenance of normal levels of GyK activity and for the enzyme response to situations, such as cold exposure, which markedly increase BAT sympathetic flow.

Brown adipose tissue glyceroneogenesis is activated in rats exposed to cold

“…It was also found in this study that glyceroneogenic activity is even higher in rats adapted to the HP diet [7]. These animals have, in addition to low levels of BAT GyK [19], a reduced uptake and utilization of glucose [18], which we have shown to be due to the combined effects of low levels of insulin [20] and a reduced BAT sympathetic activity [8]. This raised the possibility that, because of the prolonged absence of carbohydrate in the diet of HP rats, the increase in glyceroneogenic activity represented a compensatory mechanism for the reduced production of G3P from glucose and glycerol, caused by the decreases in glycolysis and GyK activity.…”

“…From the results of previous studies, which included BAT hemidenervation experiments [12,19], we concluded that whereas GyK is under direct sympathetic control, BAT glyceroneogenic flux seems to be predominantly controlled by hormonal/metabolic factors. The available evidence strongly suggests that two factors are especially important: insulin and preformed fatty acids.…”

“…Because BAT lipolysis and glycerokinase activity are stimulated by cold [12,16,19], the actual increases in glyceride-glycerol synthesis are certainly higher than those indicated by the data in Table 1, which do not include glyceride-glycerol formed by direct phosphorylation of glycerol by glycerokinase (see legend to Table 1). On the other hand, the data clearly show that, in spite of the increased utilization of glucose for glycerol synthesis, cold exposure induced a marked (four times) increase in BAT glyceride-glycerol formation from non-glucose sources (glyceroneogenesis; Table 1, Fig.…”

“…To elucidate the mechanisms of control of BAT G3P generation and improve our understanding of BAT functioning, we have recently examined the interrelated changes in the three above pathways in different physiological conditions [12,13,19]. We demonstrated that BAT GyK is under direct control by the sympathetic nervous system, its activity and expression changing in parallel to increases (cold exposure, infusion of badrenergic agents) or decreases [adaptation to a high protein, carbohydrate-free (HP) diet, BAT denervation] in sympathetic flow [12,19].…”

“…We demonstrated that BAT GyK is under direct control by the sympathetic nervous system, its activity and expression changing in parallel to increases (cold exposure, infusion of badrenergic agents) or decreases [adaptation to a high protein, carbohydrate-free (HP) diet, BAT denervation] in sympathetic flow [12,19].…”