Browning white fat to treat obesity

Brown adipose tissue (BAT) is a specialised organ that can generate heat in response to cold exposure. This thermogenic property is conferred upon BAT by a unique protein, called uncoupling protein 1 (UCP1). When activated, UCP1 allows brown fat cells to become less efficient, so that they can generate heat. Under cold-adapted conditions, activated BAT can burn more energy than any other organ in the body (per gram of weight), much more than the heart or skeletal muscle.

Recent advances in metabolic imaging have shown that most human adults possess active BAT. Although these deposits are quite small (<50g), it has been estimated that activating BAT could increase resting daily energy expenditure by up to 20%. BAT could also be used to normalise the elevated concentrations of glucose and lipids in the circulation of overweight or obese people.

Independently of BAT, fat cells (adipocytes) identical to those in BAT have also been identified in depots of white adipose tissue (WAT). WAT is the most prevalent type of adipose tissue in mammals. Under certain conditions, such as cold exposure or stimulation of the sympathetic nervous system, a proportion of the adipocytes in WAT can be converted into brown-like ('beige' or 'brite') adipocytes that are capable of generating heat. These beige/brite adipocytes are thought to confer protection against diet-induced obesity, however, their specific contribution to overall energy balance and metabolism has not been determined.

Our overall aim is remodel WAT in order to treat obesity and resolve glucose intolerance and insulin resistance. Beige/brite adipocytes represent an important therapeutic target for drugs that could increase resting energy expenditure.