Impact of Adaptive Thermogenesis in Mice on the Treatment of Obesity

Abstract

Obesity and associated metabolic diseases have become a priority area of study due to the exponential increase in their prevalence and the corresponding health and economic impact. In the last decade, brown adipose tissue has become an attractive target to treat obesity. However, environmental variables such as temperature and the dynamics of energy expenditure could influence brown adipose tissue activity. Currently, most metabolic studies are carried out at a room temperature of 21 °C, which is considered a thermoneutral zone for adult humans. However, in mice this chronic cold temperature triggers an increase in their adaptive thermogenesis. In this review, we aim to cover important aspects related to the adaptation of animals to room temperature, the influence of housing and temperature on the development of metabolic phenotypes in experimental mice and their translation to human physiology. Mice studies performed in chronic cold or thermoneutral conditions allow us to better understand underlying physiological mechanisms for successful, reproducible translation into humans in the fight against obesity and metabolic diseases.

Dietary Options for Rodents in the Study of Obesity

“…Currently, most of the metabolic and obesity studies are carried out at room temperature of 21 • C, which is considered the thermoneutral zone for adult humans. However, mice subjected to the same temperatures experience a chronic cold, because their thermoneutral zone is 30 • C [137]. It has been reported that mice show differences in metabolic phenotype when housed at room temperature (Ta) (21 • C) vs. at thermoneutrality (30 • C).…”

“…It has been reported that mice show differences in metabolic phenotype when housed at room temperature (Ta) (21 • C) vs. at thermoneutrality (30 • C). Chronic cold triggers controlled hypothermia and energy expenditure is affected by changes at the physiological (food intake, adipose tissue physiology, and increased adaptive thermogenesis) and metabolic (such as basal metabolism, adaptive thermogenesis, dietary efficiency, insulin secretion, adipose tissue physiology, adipocyte, and vascular inflammation) levels [137]. During exposure to chronic cold (21 • C), total energy expenditure may increase by more than one third, due to the cold-induced thermogenesis required to maintain basal temperature [138].…”

“…In rodents, total energy expenditure is the sum of BMR, physical activity, food thermogenesis, and cold-induced thermogenesis (facultative or adaptive) [151]. During exposure to chronic cold (21 • C), total energy expenditure may increase by more than a third, due to the cold-induced thermogenesis required to maintain basal temperature [137]. Energy homeostasis is strictly regulated by hormones that have a fundamental role in the regulation of thermogenesis [152].…”

AMPK and the Need to Breathe and Feed: What’s the Matter with Oxygen?

“…As one might expect, adaptive thermogenesis is triggered by cold both at sea level and altitude, and this is partly governed by those sympathetic pathways described above, which will also impact breathing, feeding and food choice, other than through energy expenditure pathways that may promote weight loss indirectly (for review see [149]). Moreover, during acclimation to altitude it is evident that there are differences between acute and chronic adaptive changes to breathing, feeding and food choice.…”

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

“…It is therefore highly important to elucidate the complex pathways of energy homeostasis in order to develop approaches to counteract these dysregulations of metabolism. In addition to advocating individual responsibility regarding energy intake and expenditure, which may present particularly difficult in highly obese individuals 3 , 4 , an endogenous increase of energy expenditure proposes a potential strategy. Regarding this, activation and recruitment of brown adipose tissue (BAT) thermogenesis have been discussed recently 5 – 8 .…”