Targeting energy expenditure in muscle as a means of combating obesity.

1. To date, an effective therapeutic agent that induces weight loss in obese subjects remains elusive. In order to establish a successful means to combat obesity, it is imperative that we identify novel targets that regulate energy balance. 2. Exciting new data have created resurgence in interest in the role of thermogenesis in energy balance. Recently, it has been demonstrated that functional brown adipocytes are present in adult humans and that brown adipocytes and myocytes are derived from a similar cell lineage and are thus likely to have similar physiological functions. 3. Recent work in the sheep has demonstrated that diffuse fat beds and skeletal muscle exhibit thermogenic properties. Furthermore, in sheep, central administration of leptin markedly increases postprandial thermogenesis in both fat and muscle tissues. This demonstrates that thermogenic processes in skeletal muscle can be manipulated in a similar way to thermogenesis in brown fat. 4. Given that skeletal muscle comprises a significant portion of bodyweight, approximately 30-40% of total body mass, we predict that energy expended by this tissue is likely to have significant ramifications for the regulation of bodyweight. 5. We propose that manipulation of skeletal muscle thermogenesis may provide a novel avenue for the development of anti-obesity therapies.