MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance

Abstract

The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT activity in humans is stimulated by cold exposure and by several factors such as diet and metabolic hormones. BAT function is regulated at two levels: an acute process involving the stimulation of the intrinsic thermogenic activity of brown adipocytes and a chronic process of growth involving the proliferation of pre-existing brown adipocytes or differentiation to brown adipocytes of adipocytes from specific white adipose tissue depots. BAT activity is reduced in the obese, and its stimulation by cold exposure increases insulin sensitivity and reduces body fat. These observations provide strong evidence that BAT plays a significant role in energy balance in humans and has the potential to be harnessed as a therapeutic target for the management of obesity.

Potential circadian and circannual rhythm contributions to the obesity epidemic in elementary school age children

“…Energy expenditure decreases during sleep and as a result it may seem counterintuitive that shortening of the sleep or the biological night would lead to weight gain [89]. However, in humans, the biological night is characterized by high levels of melatonin which plays a role in the timing of lipid oxidation (i.e., utilization of energy stored in adipose tissue), and brown fat thermogenesis (i.e., the conversion of fatty acids and glucose into heat) [89][90][91]. The biological day in humans is characterized by the absence of melatonin, contributing to processes involved in carbohydrate metabolism leading to lipogenesis (i.e., the creation of lipids) and storage of energy as fat in the fat cell [92,93].…”

Glucocorticoids suppress brown adipose tissue function in humans: A double‐blind placebo‐controlled study

“…There is increasing evidence that BAT contributes significantly to adiposity and substrate metabolism in humans. 17 Increase in BAT activity has led to fat loss of approximately 0.7 kg over 6 weeks, 49 amounting to approximately 6 kg over 12 months, and improvements in glycaemic status 50 and insulin sensitivity over 4 to 6 weeks. 51,52 The observed 50% reduction in BAT activity induced by 15 mg/d prednisolone may translate into a gain in fat mass of approximately 3 kg per year.…”

“…[12][13][14][15][16] There is also cumulating evidence that BAT plays a significant role in energy and substrate metabolism. 17 Energy is produced from the oxidation of substrates to sustain mammalian life. 18 Chemical energy (ATP) and heat are 2 different forms of energy that constitute the total energy produced during substrate oxidation; ATP is the energy form useful to perform body functions, 18 while heat is the energy wasted in the presence of active UCPs.…”

Mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled cross‐over study

“…Brown adipose tissue (BAT) is a thermogenic energy‐dissipating organ that protects against hypothermia and obesity in animals . There is increasing evidence that BAT plays an important role in energy balance in humans . Cold temperature is a powerful stimulus of BAT function, with prolonged exposure improving insulin sensitivity and reducing fat mass .…”

“…8 There is increasing evidence that BAT plays an important role in energy balance in humans. 9 Cold temperature is a powerful stimulus of BAT function, with prolonged exposure improving insulin sensitivity 10,11 and reducing fat mass. 12 As cold exposure is unlikely to be widely accepted, there is major interest in developing pharmacological therapies to stimulate BAT function for the management of obesity.…”