The aim of this project is to “brown” and activate human adipose tissue to increase energy expenditure for the treatment of obesity and diabetes. To determine the whole-body effects of browning agents on energy balance and glucose and fat handling (metabolism) in mice which have receive human fat transplants. Obesity occurs when energy intake exceeds energy expenditure and two-thirds of Australian adults are now overweight or obese. Rodents are known to possess significant quantities of brown adipose tissue (BAT) a thermogenic organ with an unique protein; uncoupling protein 1 (UCP1). When activated, UCP1 allows brown fat cells to generate heat and can burn more energy than any other organ in the body (per gram of weight). Recent metabolic imaging have shown that most human adults possess small amounts of BAT (<50g). It has been estimated that activation of BAT could increase resting daily energy expenditure by up to 20% and improve blood glucose (diabetes) and lipids in the circulation of overweight people. Thus, BAT represents an important therapeutic target for drugs that could increase resting energy expenditure to treat obesity and related diseases. These experiments will involve pharmacological treatment of mice (which have been transplanted with human Fat) and energy expenditure, glucose and lipid metabolism measured. The mice are given an intervention to investigate agents which may increase browning or activation of human fat. Target agents may include exercise, cold exposure, diet manipulation, ß3-Adrenergic Receptor Agonists, anti-inflammatory pharmacology and alteration of gut microflora.