Figure 4. Approaches to increasing thermogenesis as an anti-obesity therapy.

Based on the current knowledge of bioenergetics, four potential therapeutic approaches could be envisioned: (1) increasing brown fat differentiation from progenitor cells, (2) activating brown fat thermogenesis, (3) promoting skeletal muscle thermogenesis: or (4) increasing general mitochondrial uncoupling. For skeletal muscle, there are three types of thermogenesis: exercise-induced thermogenesis, non-exercise activity thermogenesis, and cold-induced shivering thermogenesis. Thus, therapeutic interventions that mimic these mechanisms could potentially increase muscle’s thermogenic capacity and counteract obesity. This is especially beneficial to individuals with physical limitations in exercising or those who are genetically predisposed to obesity. All of these approaches can be applied in the conventional pharmaceutical approaches of developing drugs and/or using natural food components targeting key pathways of cellular bioenergetics. Alternatively, there is a cell-based therapy where progenitors are isolated from patients during liposuction or biopsy, manipulated ex vivo by treating them with factors that promote BAT differentiation or transfecting them with genes specifying BAT differentiation, then transplanted these cells back into the same individual to generate a functional brown fat to help dissipate excess energy.