Perspective: Promoting metabolic inefficiency for metabolic disease

Recent advances in pharmacotherapies that promote appetite suppression have shown remarkable weight loss. Therapies targeting energy expenditure lag behind, and as such none have yet been identified to be safe and efficacious for sustaining negative energy balance toward weight loss. Multiple energy dissipating pathways have been identified in adipose tissue and muscle. The molecular effectors of some of these pathways have been identified, but much is still left to be learned about their regulation. Understanding the molecular underpinnings of metabolic inefficiency in adipose tissue and muscle is required if these pathways are to be therapeutically targeted in the context of obesity and obesity-accelerated diseases.