Novel pharmacological approaches to combat obesity and insulin resistance: targeting skeletal muscle with ‘exercise mimetics’

Chronic diseases arising from obesity will continue to escalate over coming decades. Current approaches to combating obesity include lifestyle measures, surgical interventions and drugs that target weight reduction or the metabolic consequences of obesity. Lifestyle measures including physical activity are usually the primary strategy, but these are of limited long-term efficacy because of failure to maintain behavioural change. An alternative approach used to elicit the benefits of exercise training and overcome the problems of long-term compliance is to develop drugs that mimic aspects of the trained state. Elucidation of metabolic pathways responsive to exercise in various tissues, particularly skeletal muscle, was an important antecedent to the promising concept of drugs that may mimic specific aspects of the exercise response. From an obesity perspective, an important aim is to develop an agent that reduces body fat and improves metabolic homeostasis. This review focuses on promising metabolic signalling pathways in skeletal muscle that may yield ‘exercise mimetic’ targets.