Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2013-07, Vol.65 (5), p.549-557
• Main Authors: Slocum, Nikki, Durrant, Jessica R., Bailey, David, Yoon, Lawrence, Jordan, Holly, Barton, Joanna, Brown, Roger H., Clifton, Lisa, Milliken, Tula, Harrington, Wallace, Kimbrough, Carie, Faber, Catherine A., Cariello, Neal, Elangbam, Chandikumar S.
• Format: Article
• Language: English
• Subjects: adipocytes; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, Brown - pathology; adverse effects; Animals; Body Composition - drug effects; body fat; Body Weight - drug effects; Brown adipose tissue; Caloric Restriction; Diet-induced obese mice; Dietary Fats - administration & dosage; dietary restriction; Energy Metabolism - drug effects; ephedrine; Ephedrine - administration & dosage; Ephedrine - adverse effects; Ephedrine - therapeutic use; exercise; fatty acids; Gene expression; Gene Expression - drug effects; gene expression regulation; genes; hepatocytes; histopathology; humans; lifestyle; liver; Liver - drug effects; Liver - metabolism; low calorie diet; Male; messenger RNA; Mice; Mice, Inbred Strains; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial Proteins - biosynthesis; Mitochondrial Proteins - genetics; Motor Activity - drug effects; Motor Activity - physiology; Obesity; Obesity - etiology; Obesity - metabolism; Obesity - pathology; Obesity - prevention & control; oxygen consumption; Oxygen Consumption - drug effects; Sympathomimetics - administration & dosage; Sympathomimetics - adverse effects; Sympathomimetics - therapeutic use; Thermogenesis; weight loss
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2012.04.001

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 (18mg/kg/day orally), treadmill exercise (10m/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 (VO2ml/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.