Brown adipose tissue thermogenesis in the resistance to and reversal of obesity: A potential new mechanism contributing to the metabolic benefits of proglucagon-derived peptides

The capacity for increased thermogenesis through brown adipose tissue (BAT) activation is important for body weight homeostasis. Differences in BAT thermogenesis can underlie significant differences in body weight and body composition, as we demonstrate in a rat model of obesity. This mini-review focuses on our current understanding of physiological BAT regulation, with a view to how it may be exploited therapeutically. BAT activation is under central nervous system control, with the most potent activator of BAT being the sympathetic nervous system, although other humoral and hormonal factors also contribute to BAT regulation. The peptide products of the proglucagon gene are important in energy homeostasis, with well-described effects on feeding and body weight. We recently demonstrated that the peptides glucagon-like peptide 1, glucagon, and oxyntomodulin are also able to induce BAT thermogenesis by a central, sympathetic mechanism. Given the wide spread use of GLP-1 receptor based therapies for type 2 diabetes, drugs targeting this system may be useful in a wider energy balance context.