Abstract
Background: Cold-activated brown adipose tissue (BAT) in humans is associated with improved insulin sensitivity and lipid metabolism, at least in lean individuals (1). Metabolic effects of acute cold-induced BAT activation in obese individuals are less characterized. Here, we studied the effects of acute cold-induced BAT activation on energy metabolism and aimed to identify underlying transcriptional mechanisms in obese males. Methods: Fourteen metabolically healthy obese subjects (age 25.3±0.8 years; BMI 32.6±0.92 kg/m(2)) participated in a cross-balanced within-subject study, with two experimental conditions. Using a water-perfused suit, subjects were exposed to thermoneutrality (25°C) and to moderate cold (16.07°C, shivering excluded) according to a protocol validated for BAT activation. Glucose and lipid metabolism as well as relevant hormones were measured. Glucose tolerance and insulin sensitivity were assessed by Botnia clamp. Moreover, the expression of 7 selected genes within lipolytic and β-oxidation pathways (i.e. PDK4, CPT1α and CPT1β, G0S2, FFAR4, SLC25A20 and PPARα) were determined from circulating blood cells. Major results: Upon moderate cold exposure, noradrenaline and dopamine markedly increased relative to thermoneutrality (p<0.001 and p=0.008, respectively), while fT(4) decreased (p=0.012). Compared to thermoneutrality, fasting glucose was significantly decreased upon moderate cold exposure (p=0.03). The AUC of plasma glucose was reduced following the glucose challenge (total AUC p=0.009) and larger concentrations of serum insulin were found both during the first 30 minutes of the ivGTT and over its entire duration (AUC t0-t30 p=0.002, total AUC p<0.001). Circulating TG were increased upon exposure to moderate cold (p=0.034) but no changes were observed in total cholesterol, HDL or LDL (all p>0.442). Moderate cold increased relative expression levels of PDK4, CPT1α, SLC25A20 and G0S2 (p=0.006, p=0.017, p=0.041 and p=0.002, respectively) but no changes were observed for CPT1β, FFR4 and PPARα expressions (all p>0.065). Results interpretation and conclusion: Acute cold-induced BAT activation exerts beneficial effects on glucose metabolism in obese subjects although not on insulin sensitivity, as described in normal weight humans (2). Furthermore, here we showed that these effects might be fostered by a shift towards lipolysis and β-oxidation pathways. Reference: (1) Betz MJ et al., Diabetes. 2015;64(7):2352-60. (2) Iwen KA et al., JCEM. 2017;102(11):4226-4234 Sources of Research Support: Deutsche Forschungsgemeinschaft, project GRK1957 Adipocyte-Brain Crosstalk (grant to SMS)