The incidence of the metabolic syndrome has reached epidemic levels in the western world. With respect to the energy balance most attention has been given to reducing energy (food) intake. Increasing energy expenditure is an important alternative strategy. Adaptive thermogenesis, which is the increase in energy expenditure in response to cold or diet, may be an effective way to affect the energy balance.
Several studies have confirmed that humans show significant (mild) cold induced thermogenesis, i.e. without shivering. The individual variation in CIT is large. There are indications that CIT is reduced in obese subjects. Tissues shown to be involved in adults are skeletal muscle and brown adipose tissue (BAT). The most likely cellular mechanism in both tissues is mitochondrial uncoupling.
At the functional level, adipocytes can be subdivided into white and brown. The most important function of white adipocytes is energy storage, while the main function of brown adipocytes is heat production. Brown adipocytes are located in distinct BAT depots, in white adipose tissue (BRITE adipocytes), or in skeletal muscle tissue (BRUSCLE adipocytes).
Intriguingly, functional and active BAT is inversely correlated with age and body mass index (BMI) in humans. Indeed, thermogenic BAT is a major site for lipid breakdown and glucose uptake, and thus the thermogenic capacity of even small amounts of brown adipocytes has emerged as an attractive target for anti-diabesity therapies.
Animal and human studies indicate that recruitment and activation of brown and brite adipocytes can potentially be accomplished by pharmacological, nutritional or environmental intervention. Crucial in the activation of adaptive thermogenesis and brown adipocytes are the sympathetic nervous system and the thyroid hormone axis. In stimulating thermogenesis and BAT activity, thyroid hormone works synergistically with the sympathetic nervous system at different levels.