Abstract
The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and exercise training are two stimuli that have been investigated with respect to BAT activation, metabolism, and the contribution of BAT to metabolic health. These two stimuli are of great interest because they have both disparate and converging effects on BAT activation and metabolism. Cold exposure is an effective mechanism to stimulate BAT activity and increase glucose and lipid uptake through mitochondrial uncoupling, resulting in metabolic benefits including elevated energy expenditure and increased insulin sensitivity. Exercise is a therapeutic tool that has marked benefits on systemic metabolism and affects several tissues, including BAT. Compared to cold exposure, studies focused on BAT metabolism and exercise display conflicting results; the majority of studies in rodents and humans demonstrate a reduction in BAT activity and reduced glucose and lipid uptake and storage. In addition to investigations of energy uptake and utilization, recent studies have focused on the effects of cold exposure and exercise on the structural lipids in BAT and secreted factors released from BAT, termed batokines. Cold exposure and exercise induce opposite responses in terms of structural lipids, but an important overlap exists between the effects of cold and exercise on batokines. In this review, we will discuss the similarities and differences of cold exposure and exercise in relation to their effects on BAT activity and metabolism and its relevance for the prevention of obesity and the development of type 2 diabetes.
Highlights
The overall prevalence of obesity has increased dramatically over the last several decades [1,2].The World Health Organization (WHO) has reported that more than 1.9 billion adults around the world are overweight and nearly one-third of the population is obese [3]
Exercise increased the expression of genes involved in glucose metabolism in Brown adipose tissue (BAT), but brown adipocytes differentiated from the stromal vascular fraction (SVF) isolated from exercise-trained BAT had decreased basal glucose uptake compared to brown adipocytes differentiated from sedentary BAT [73] (Table 1)
A study of cold acclimation in healthy humans (15 ◦ C–16 ◦ C, 2 h to 6 h/day, 10 days) did not show beiging of scWAT [160]. These disparities in the results are likely associated with the duration of cold exposure. While it seems that long term cold exposure can promote beiging of scWAT in humans, further studies are needed to define the length of cold exposure needed to induce beiging in humans, and whether these observations can be translated to subjects with obesity and T2DM
Summary
The overall prevalence of obesity has increased dramatically over the last several decades [1,2]. Cold exposure leads to the activation of the sympathetic nervous system (SNS), causing release of norepinephrine from sympathetic nerves and activation of the β-adrenergic receptor (β-AR) This stimulates cyclic adenosine monophosphate (cAMP)-dependent signaling pathways and results in increased fuel uptake and oxidation for heat generation by UCP1 [24]. In this review, we will discuss the current literature examining the effects of cold exposure and exercise on BAT activation and energy expenditure with a focus on how they impact glucose metabolism, lipid metabolism, structural lipids, and BAT-secreted factors (batokines) in terms of their similarities, differences, and potential relevance for the prevention of obesity and T2DM (Figure 1).
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