Editorial: current challenges for targeting brown fat thermogenesis to combat obesity

Abstract

Just over a decade has passed since metabolically active brown adipose tissue (BAT) was unequivocally identified in healthy adult humans. Since then, researchers have provided evidence of expression of the thermogenic molecule uncoupling protein 1 (UCP1) in human BAT, as well as its energy dissipating capacity. Additionally, clinical cross-sectional analysis suggested that a decline in BAT activity with aging, as judged from [18F]FDG-PET/CT, coincides with the development of obesity and insulin resistance. These major observations provided a rationale to investigate BAT as a potential target for preventing obesity. Indeed, several studies have demonstrated that cold exposure and adrenomimetic agents strongly activate BAT thermogenesis, and thus energy expenditure in humans. However, the extent to which stimulating BAT thermogenesis decreases adiposity in humans remains unclear. Moreover, therapeutic strategies aimed at general stimulation of the sympathetic nervous system (SNS) and adrenergic receptors involved may not be applicable for obese and diabetic patients, because of potential negative side-effects on cardiovascular function. While implementation in humans remains challenging, recent studies in mice have yielded insights in molecular mechanisms underlying thermogenic regulation of brown and brown-like (brite/beige) adipocytes, highlighting their ability to reduce insulin resistance and atherosclerosis (1). These include identification of UCP1-independent thermogenesis as well as peripheral organ-derived endocrine factors and metabolites capable of triggering adipocyte thermogenesis. Activating these non-canonical mechanisms through genetic manipulation or pharmacological agents suppresses obesity and its associated complications in mice. The major challenge remains translating preclinical scientific advances to humans. To bridge basic research with clinical investigation, this Research Topic reviews the current advances in human BAT pathophysiology, novel molecular mechanisms regulating adipose thermogenesis, and remaining challenges in this field.