title: The Therapeutic Potential of Brown Adipocytes in Humans.
abstract: Obesity and its metabolic consequences represent a significant clinical problem. From a thermodynamic standpoint, obesity results from a discord in energy intake and expenditure. To date, lifestyle interventions based on reducing energy intake and/or increasing energy expenditure have proved ineffective in the prevention and/or treatment of obesity, owing to poor long-term adherence to such interventions. Thus, an effective strategy to prevent or correct obesity is currently lacking. As the combustion engines of our cells, mitochondria play a critical role in energy expenditure. At a whole-body level, approximately 80% of mitochondrial membrane potential generated by fuel oxidation is used to produce ATP, and the remaining 20% is lost through heat-producing uncoupling reactions. The coupling of mitochondrial respiration to ATP production represents an important component in whole-body energy expenditure. Brown adipose tissue (BAT) is densely populated with mitochondria containing the inner mitochondrial proton carrier uncoupling protein 1 (UCP1). UCP1 uncouples oxidative phosphorylation, meaning that mitochondrial membrane potential is dissipated as heat. The recent rediscovery of BAT depots in adult humans has rekindled scientific interest in the manipulation of mitochondrial uncoupling reactions as a means to increase metabolic rate, thereby counteracting obesity and its associated metabolic phenotype. In this article, we discuss the evidence for the role BAT plays in metabolic rate and glucose and lipid metabolism in humans and the potential for UCP1 recruitment in the white adipose tissue of humans. While the future holds much promise for a therapeutic role of UCP1 expressing adipocytes in human energy metabolism, particularly in the context of obesity, tissue-specific strategies that activate or recruit UCP1 in human adipocytes represent an obligatory translational step for this early promise to be realized.
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children-Galveston , Galveston, TX , USA ; Department of Surgery, University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Porter
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children-Galveston , Galveston, TX , USA ; Department of Preventive Medicine and Community Health, University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Chondronikola
authors.affiliation: Metabolism Unit, Shriners Hospitals for Children-Galveston , Galveston, TX , USA ; Department of Surgery, University of Texas Medical Branch , Galveston, TX , USA ; Department of Nutrition and Dietetics, Harokopio University of Athens , Athens , Greece ; Department of Internal Medicine, University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Labros S
authors.initials: LS
authors.lastname: Sidossis
keywords: adipose tissue; mitochondria; obesity; thermogenesis; uncoupling protein 1