Drug-induced
weight loss in humans has been associated with undesirable side effects not present in
weight loss from lifestyle interventions (
caloric restriction or exercise). To investigate the mechanistic differences of
weight loss by drug-induced and lifestyle interventions, we examined the gene expression (
mRNA) in brown adipose tissue (BAT) and conducted histopathologic assessments in diet-induced obese (DIO) mice given
ephedrine (18 mg/kg/day orally), treadmill exercise (10 m/min, 1-h/day), and
dietary restriction (DR: 26%
dietary restriction) for 7 days. Exercise and DR mice lost more
body weight than controls and both
ephedrine and exercise reduced percent body fat. All treatments reduced BAT and liver
lipid accumulation (i.e., cytoplasmic
lipids in brown adipocytes and hepatocytes) and increased oxygen consumption (VO2 ml/kg/h) compared with controls. Mitochondrial biogenesis/function-related genes (TFAM, NRF1 and GABPA) were up-regulated in the BAT of all groups. UCP-1 was up-regulated in exercise and
ephedrine groups, whereas MFSD2A was up-regulated in
ephedrine and DR groups. PGC-1α up-regulation was observed in exercise and DR groups but not in
ephedrine group. In all experimental groups, except for
ephedrine,
fatty acid transport and metabolism genes were up-regulated, but the magnitude of change was higher in the DR group. PRKAA1 was up-regulated in all groups but not significantly in the
ephedrine group. ADRß3 was slightly up-regulated in the DR group only, whereas ESRRA remained unchanged in all groups. Although our data suggest a common pathway of BAT activation elicited by
ephedrine treatment, exercise or DR,
mRNA changes were indicative of additional nutrient-sensing pathways in exercise and DR.