Ion transport and brown adipose tissue activity in energy balance.

Abstract

The objective of this work was to study the activity of the Na$\sp+$,K$\sp+$ pump and the thermogenic activity and capacity of brown adipose tissue (BAT) under conditions of dietary energy deficit and surfeit in both human subjects and laboratory animals. While controversial, it had earlier been hypothesized that Na$\sp+$,K$\sp+$ pump activity (1) acts as a "metabolic pacemaker" in the control of cellular energy expenditure, and (2) "adapts" during undernutrition so that overall energy expenditure is decreased. That BAT thermogenic activity increases during overfeeding and decreases during undernutrition is well recognised; BAT thermogenesis has hence been proposed as an "energy buffer" mechanism. However, at the outset of this work the effectiveness of dietary saturated fat in the induction of BAT thermogenesis was controversial. The first sections of this thesis describe the effects of undernutrition and nutritional rehabilitation upon Na$\sp+$,K$\sp+$ pump activity in erythrocytes of children with cerebral palsy (CP). The results show that, unlike results from developing world undernourished children, erythrocyte Na$\sp+$,K$\sp+$ pump activity was not lower in cells from the undernourished children with CP. The later sections describe the simultaneous study of both Na$\sp+$,K$\sp+$ pump and BAT activities during diet-induced obesity (DIO) and dietary restriction (DR) in rats. I hypothesized that both mechanisms might act as "energy buffers" and contribute to metabolic adaptation during DIO and DR. The effects of lard- and tallow-based diets were studied. The extent of DIO was assessed using total body electrical conductivity (TOBEC), carcass analysis and fat pad weights; it was concluded that presently available TOBEC equipment is unsuitable for serial determinations of rat adiposity, and that fat pad weights are good estimates of adiposity. Na$\sp+$,K$\sp+$ pump activity increased in thymocytes of rats fed the high saturated fat diets; activity decreased in erythrocytes and hepatocytes in some groups following DR. BAT activity and thermogenic capacity were enhanced by high saturated fat diet-feeding; activity decreased following DR. Lard- and tallow-based diets had differing effects upon the extent and the timing of changes in the activities of the two mechanisms. Despite increases in Na$\sp+$,K$\sp+$ pump and BAT activities, basal metabolic rate (BMR) was not increased in the obese rats; decreases did however occur following DR. Diet-induced alterations in both mechanisms could occur through common pathways such as sympathetic neural activity and/or thyroid hormones. Increases in plasma T$\sb3$ concentrations were associated with high saturated fat diet feeding as were decreases with DR. It is concluded that the alterations in both mechanisms are compatible with the hypothesis that these mechanisms function as energy buffer mechanisms during dietary energy surfeit and deficit.