Dysfunction and therapeutic potential of brown adipose tissue and batokines in obesity and type 2 diabetes mellitus

This is the authors' abstract. We don't add key points for this paper.

Obesity and Type 2 Diabetes Mellitus (T2D) remain key drivers of premature mortality, morbidity, and healthcare expenditure globally. Although we have witnessed dramatic recent advances in our therapeutic armamentarium for these conditions (most notably regarding the latest iterations of the Glucagon-like Peptide-1 [GLP-1] class of therapies), there remain important unmet needs in our current management approach. Brown adipose tissue (BAT) and its associated batokines (molecules release from BAT) plays a key role in the regulation of energy expenditure and glucose and lipid metabolism. Multiple lifestyle factors (most notably cold exposure and certain nutrients) can activate BAT via activation of the systemic nervous system (SNS). In the context of obesity and T2D, BAT activity is downregulated through multiple complex processes. This downregulation further promotes insulin resistance and dysregulation of metabolic regulation that contributes towards ongoing pathogenesis of these pernicious conditions, in a vicious circle. In such a scenario, it would be desirable to break this vicious circle through novel therapies that target the BAT-batokine axis. In recent times, there has been a transformation of our insights into this approach, particularly from data derived from rodent models. Beyond facilitating weight loss and improved metabolic efficiency and flexibility, such a novel approach to therapy that targets the BAT-batokine axis would improve glucose and lipid regulation but also have potential for organ-specific therapeutic benefits, including in the heart, lung, kidney, and liver. Furthermore, such an approach holds great promise to improve body composition (to reduce adiposity whilst preserving or even enhancing skeletal muscle mass and function), due to the therapeutic effects being independent of negative energy balance. The BAT-batokine axis has finally come of age.