Brown Fat and Obesity: The Next Big Thing?
Brown Fat and Obesity: The Next Big Thing?
Brown adipose tissue (BAT) is well recognised to have an important role in the maintenance of body temperature in animals and human neonates, its thermogenic action affected by a tissue-specific uncoupling protein; fatty acid oxidation within the numerous brown adipocyte mitochondria is rendered inefficient leading to heat, rather than adenosine triphosphate (ATP), production. BAT was believed to show rapid involution in early childhood, leaving only vestigial amounts in adults. However, recent evidence suggests that its expression in adults is far more common than previously appreciated, with a higher likelihood of detection in women and leaner individuals. It is conceivable that BAT activity might reduce the risk of developing obesity since fat stores are used for thermogenesis, and a directed enhancement of adipocyte metabolism might have value in weight reduction. However, it is as yet unclear how such manipulation of BAT might be achieved; even in animal models, the control of thermogenic activity is incompletely understood. Even so, there is still much to interest the endocrinologist in BAT, with a range of hormones affecting adipocyte activity. This may either contribute to normal physiological function, or the phenotypical presentation of states of pathological hormone excess or deficiency. Thus, the gender differences in BAT distribution may be attributable to the differential effects of male and female sex hormones, whilst BAT expansion may drive the weight loss associated with catecholamine-producing phaeochromocytomas. These observations support an important influence of the endocrine system on BAT activity and offer new potential targets in the treatment of obesity.
Obesity is a major global public health challenge. The prevalence of obesity has reached epidemic proportions and is expected to rise further, such that the latest projections estimate that 2·16 billion overweight and 1·12 billion obese individuals will be affected globally by 2030. In addition to increased social stigmatization, financial disadvantage and impaired quality of life, obese individuals are faced with a markedly increased risk of cardiovascular disease, type 2 diabetes, osteoarthritis and a number of cancers. Lifestyle modification in the obese often provides only transient success, whilst clinical intervention has proven difficult; bariatric surgery is effective, but not without risk, and pharmaceutical options limited, especially following the recent withdrawal of both rimonabant and sibutramine within the European Union. The need for novel therapeutic approaches is therefore pressing. Brown adipose tissue (BAT), in contrast to white adipose tissue (WAT), is involved in energy dissipation rather than storage, but was previously considered to have little physiological relevance in humans beyond early childhood. However, recent studies using F-fluorodeoxyglucose (F-FDG) positron emission tomography–computed tomography (PET–CT) prove that BAT is present in adults, with activity notably declining with increasing obesity. Working within the context of clinical endocrinology, the authors ask could the recruitment of larger amounts of BAT or an enhancement of its activity be an 'antidote' to obesity?
Abstract and Introduction
Abstract
Brown adipose tissue (BAT) is well recognised to have an important role in the maintenance of body temperature in animals and human neonates, its thermogenic action affected by a tissue-specific uncoupling protein; fatty acid oxidation within the numerous brown adipocyte mitochondria is rendered inefficient leading to heat, rather than adenosine triphosphate (ATP), production. BAT was believed to show rapid involution in early childhood, leaving only vestigial amounts in adults. However, recent evidence suggests that its expression in adults is far more common than previously appreciated, with a higher likelihood of detection in women and leaner individuals. It is conceivable that BAT activity might reduce the risk of developing obesity since fat stores are used for thermogenesis, and a directed enhancement of adipocyte metabolism might have value in weight reduction. However, it is as yet unclear how such manipulation of BAT might be achieved; even in animal models, the control of thermogenic activity is incompletely understood. Even so, there is still much to interest the endocrinologist in BAT, with a range of hormones affecting adipocyte activity. This may either contribute to normal physiological function, or the phenotypical presentation of states of pathological hormone excess or deficiency. Thus, the gender differences in BAT distribution may be attributable to the differential effects of male and female sex hormones, whilst BAT expansion may drive the weight loss associated with catecholamine-producing phaeochromocytomas. These observations support an important influence of the endocrine system on BAT activity and offer new potential targets in the treatment of obesity.
Introduction
Obesity is a major global public health challenge. The prevalence of obesity has reached epidemic proportions and is expected to rise further, such that the latest projections estimate that 2·16 billion overweight and 1·12 billion obese individuals will be affected globally by 2030. In addition to increased social stigmatization, financial disadvantage and impaired quality of life, obese individuals are faced with a markedly increased risk of cardiovascular disease, type 2 diabetes, osteoarthritis and a number of cancers. Lifestyle modification in the obese often provides only transient success, whilst clinical intervention has proven difficult; bariatric surgery is effective, but not without risk, and pharmaceutical options limited, especially following the recent withdrawal of both rimonabant and sibutramine within the European Union. The need for novel therapeutic approaches is therefore pressing. Brown adipose tissue (BAT), in contrast to white adipose tissue (WAT), is involved in energy dissipation rather than storage, but was previously considered to have little physiological relevance in humans beyond early childhood. However, recent studies using F-fluorodeoxyglucose (F-FDG) positron emission tomography–computed tomography (PET–CT) prove that BAT is present in adults, with activity notably declining with increasing obesity. Working within the context of clinical endocrinology, the authors ask could the recruitment of larger amounts of BAT or an enhancement of its activity be an 'antidote' to obesity?
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