Brown Adipose Tissue

Abstract

O besity is a significant health challenge, with the latest projections estimating that there will be 2.16 billion overweight and 1.12 billion obese individuals globally by 2030. In addition to social stigmatization and impaired quality of life, obese people are faced with significantly increased risk of cardiovascular disease, type 2 diabetes mellitus, and a number of cancers. Weight gain results from a sustained imbalance between energy intake (calories consumed) and energy expenditure (calories burned), resulting in positive energy balance. To tip energy balance toward weight loss, not only should food intake be decreased, but increasing physical activity may help. It is important to realize, however, that the secular rises in obesity over the past 3 to 4 decades can be explained by both physiological and environmental drivers and a number of putative factors ( Figure 1). 1,2 At one level, the obesity epidemic is a classic gene-environment interaction in which the human genotype is susceptible to environmental influences that affect energy intake and expenditure, with the obesogenic environment being dominant. These environmental factors include the 2 obvious explanations, ie, reduced physical activity and increased energy intake from high-calorie food and drinks, with the latter likely being the dominant factor. 3 However, other less studied factors have been implicated, including longer time spent awake, increased mean age of mothers at first birth, decreased prevalence of smoking, presence of environmental pollutants, ingestion of many novel medications, and reduction in the variability of seasonal ambient temperature owing to the presence of almost ubiquitous air conditioning. 4 Fundamentally, the obesity epidemic is explained by a dysregulation of energy balance in our obesogenic environment. Understanding the cause of obesity requires the study of how genetic and environmental factors interact to produce long-term positive energy balance.As a consequence of the obesogenic environment, the treatment of obesity requires intensive lifestyle modification. However, lifestyle modification in obese individuals tends to provide only transient success, and pharmacological treatment of obesity has often been disappointing and is very contentious because of the many safety concerns. Other approaches such as bariatric surgery are costly and not without risk. Thus, there is a concerted effort to find novel strategies to reduce excess body weight. This includes the potential of increasing energy expenditure via the stimulation of brown adipose tissue (BAT), now known to be present in adult humans. We would expect that such physiological or pharmacological stimulation of thermogenesis (heat production) would lead to dissipation of at least some excess ingested calories. This review provides a historical overview on the research on BAT, highlights recent developments in the field, and concludes with a discussion of the relevant issues that need to be addressed before BAT is considered a therapeutic option for human obe...

Epigenetics and human obesity

“…Metabolic disturbances are often linked to increased fat deposition in visceral depots, while storage in subcutaneous depots is considered less problematic from a metabolic stand-point. Recently, there has been renewed interest in understanding the role of brown fat in humans, in particular in relation to human obesity, as a consequence of its fat burning properties 101 . Since DNA methylation is of major importance in defining cellular identity and differentiation of adipocytes, the study of DNA methylation profiles in different adipose tissue depots under different metabolic conditions could provide information about how epigenetic regulation of adipose tissue is involved in the development of obesity and associated co-morbidities, and how this could potentially be manipulated.…”

How brown is brown fat that we can see?

“…10,33,34 Recent studies in mouse models support this concept, which opens new perspectives for obesity management. 49 It must be noted, however, that inducing BAT activity in adult humans results in a relatively minor increase in energy expenditure according to a recent study. 44 This indicates that BAT activation may be insufficient for significant effects on weight, pointing to potential therapeutic limitations.…”

Brown adipose tissue: what have we learned since its recent identification in human adults

“…However, it has only been recognized as a mammal specific thermogenic organ, essential for mammalian thermoregulation, for less than half a century (2). It was believed, for the second half of the 20 th Century and the beginning of the 21 st , to only be present in the human newborn and that it began to involute throughout childhood (2,3). Although some indirect evidence had led a few authors to postulate its presence before (1,4-9), it was only when positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG), a functional imaging method that evaluates areas of greater metabolic activity, started being used more frequently in the follow-up of some cancers, that brown adipose tissue was identified in at least one subgroup of the adult human population (2,(10)(11)(12)(13)(14).…”