Cold acclimation recruits human brown fat and increases nonshivering thermogenesis

Abstract

In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans

“…Because glucose is not the primary substrate, BAT activity based on [ 18 F]FDG uptake may underestimate and potentially miss components of BAT energy metabolism under certain physiological conditions. While [ 18 F]FDG-PET-based assessments of human BAT activity in response to acute [20,21,38,42] and chronic [2,4] cold exposure have reflected the expected outcomes based on rodent experiments, this study indicates that there are species differences for other adaptive stimuli. Although we have shown that pioglitazone reduced coldstimulated BAT glucose uptake, we cannot definitively claim that fat oxidative capacity also decreased.…”

“…During this process BAT's thermogenic capacity increases such that energy expenditure in response to an equivalent stimulus is increased [1]. A recent series of studies demonstrated cold-induced adaptive BAT thermogenesis in humans [2][3][4][5]. Chronic cold exposure is not, however, likely to be tolerated in humans and is associated with increased food intake, therefore is unlikely to be successful as an anti-obesity strategy.…”

Obesity and related consequences to ageing

“…In morbidly obese human subjects, expression of UCP1 in BAT was shown to be significantly reduced in comparison to lean controls (Vijgen et al 2011). It is speculated that the absence of adequate amounts of BAT could lead to a severe overweight condition (Vijgen et al 2011;van der Lans et al 2013). However, mice with an inactive Ucp1 gene do not have increased susceptibility to DIO (Liu et al 2003), leading to an alternative interpretation that overall, metabolic efficiency is reduced in individuals with lower levels of UCP1-based thermogenesis (Butler and Kozak 2010).…”

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

“…To evaluate whether glucose uptake into BAT is impaired during fasting-induced insulin resistance, we here examined 16 young, healthy participants in which BAT glucose uptake was measured after both baseline and 54 h fasting conditions using dynamic 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) imaging under cold-stimulated conditions, in the absence of shivering [22].…”