Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

Abstract

Introduction: Brown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the β-adrenoceptor (β-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unknown. The objective of our study was to assess the in vivo BAT temperature responses to acute glucocorticoid administration.

Methods: We studied 8 healthy male volunteers, not pre-selected for BAT presence or activity and without prior BAT cold-activation, on two occasions, following an infusion with hydrocortisone (0.2mg.kg^-1.min^-1 for 14h) and saline, respectively. Infusions were given in a randomized double-blind order. They underwent assessment of supraclavicular BAT temperature using infrared thermography following a mixed meal, and during β-AR stimulation with isoprenaline (25ng.kg fat-free mass^-1.min^-1 for 60min) in the fasting state.

Results: During hydrocortisone infusion, BAT temperature increased both under fasting basal conditions and during β-AR stimulation. We observed a BAT temperature threshold, which was not exceeded despite maximal β-AR activation. We conclude that BAT thermogenesis is present in humans under near-normal conditions. Glucocorticoids modulate BAT function, representing important physiological endocrine regulation of body temperature at times of acute stress.

Keywords: Beta adrenoceptor; Brown adipose tissue; Glucocorticoids; Humans; Infrared thermography.

Fig. 1

Study design and temperature responses to a meal. Each participant underwent the study twice, whereby BAT thermogenic activity was studied with infrared thermography before and after a standardized meal, followed by either a 14 h overnight constant hydrocortisone or normal saline (control) infusion. Infusions were given in a randomized, double-blind order and continued during and after β-adrenoceptor stimulation with isoprenaline (A). Mean changes in supraclavicular region (T_SCR, gray circles) and non-adipose tissue reference (T_REF, open squares) temperatures (dotted line indicates time of meal) (B), individual responses (fasting, open squares; postprandial, black squares) (C), and changes in core temperature (fasting, open circles; postprandial, black squares) (D) following the meal. *p < 0.05 compared to fasting baseline, n = 8.

Fig. 2

Metabolic and cardiovascular responses following saline infusion (S) or hydrocortisone infusion (HC) at baseline and during an isoprenaline infusion (ISO, dotted lines indicate infusion period). Plasma cortisol concentrations (saline, open circles; hydrocortisone, black squares) (A), non-esterified fatty acids (NEFA) (saline, open circles; hydrocortisone, black squares) (B), glucose (saline, open circles; hydrocortisone, black squares) (C), supraclavicular temperature (T_SCR) (saline, open circles; hydrocortisone, black circles) (D) and core temperature at baseline (saline, open squares; hydrocortisone, black squares) (E). Systolic (sys) and diastolic (dia) blood pressure (BP) and heart rate (HR) at baseline (saline, open bars; hydrocortisone, black bars) (F). *p < 0.05 vs. control, n = 8.

Fig. 3

BAT thermogenic responses. Supraclavicular temperature (T_SCR) and non-adipose tissue reference point (T_REF) following saline (S) infusion (T_SCR, gray circles; T_REF open squares) (A) or hydrocortisone (HC) infusion (T_SCR, gray circles; T_REF open squares) (B) during and after isoprenaline stimulation (ISO, dotted lines indicate infusion period). Individual peak BAT temperatures during ISO (S, open circles; HC, black circles) (C). Change in temperature during ISO or following a standardized meal (T_SCR, gray bars; T_REF open bars) (D). *p < 0.001 vs. basal, †p < 0.05 vs. saline, #p < 0.001 vs. saline, ##p < 0.001 vs. T_REF, n = 8.