An investigation of diet-induced thermogenesis during overfeeding, thermogenic responsiveness to ephedrine administration and diet-induced thermogenesis following propranolol administration

The current obesity literature places strong emphasis upon the influence that Diet-Induced Thermogenesis (DIT) has on weight regulation and the possible mediating role of Brown Adipose Tissue (BAT) in DIT. This focus arises from animal research which establishes the significance of DIT and BAT in the energy balance of rodents. Recent studies indicate differential postprandial DIT between lean and obese individuals. The contribution of resting state DIT to energy balance is equivocal, a situation in part due to disagreement regarding the extent of excess energy needed to trigger the response, and individual differences in responding. At present, only catechol-amine stimulation studies suggest the active presence of BAT in adults. This thesis addresses four research questions arising from the obesity literature: (i) Does the DIT response to overfeeding in either post-prandial or resting state conditions show any change over five days overfeeding? (ii) Is a subject's responsiveness to a standard test of thermogenic capacity (i.e. stimulation by the sympatheticomimetic drug ephedrine) predictive of their DIT response to overfeeding? (iii) Is BAT involved in mediating the DIT response during the postprandial period? and (iv) Can the DIT response to overfeeding be blocked by the beta-adrenergic antagonist propranolol? These questions were investigated in two studies. Experiment 1, testing seven subjects, examined questions (i) to (iii), Experiment 2 examined question (iv) with the three strongest responders from the first experiment. DIT and response to sympathetic stimulation were measured through metabolic rate (02 consumption and HR) increase. BAT activity was assessed via skin temperature change at sites of probable BAT deposits. The results suggest that in certain individuals resting state DIT can be achieved following a single day's overfeeding. The data also suggest that dietary history may underpin DIT response ability. As only a positive trend was found between MR stimulated by ephedrine and overfeeding respectively, the relationship between these responses remains equivocal. The BAT hypothesis was challenged by a failure to observe skin temperature increase following both ephedrine administration and overfeeding, and the failure of propanolol to inhibit DIT. The results are interpreted as clarifying the occurrence of resting state DIT in respect to short term overfeeding, and calling into question speculation regarding BAT's role in thermogenesis