In vivo measurement of energy substrate contribution to cold‐induced brown adipose tissue thermogenesis

Abstract

The present study was designed to investigate the effects of cold on brown adipose tissue (BAT) energy substrate utilization in vivo using the positron emission tomography tracers [(18)F]fluorodeoxyglucose (glucose uptake), 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid [nonesterified fatty acid (NEFA) uptake], and [(11)C]acetate (oxidative activity). The measurements were performed in rats adapted to 27°C, which were acutely subjected to cold (10°C) for 2 and 6 hours, and in rats chronically adapted to 10°C for 21 days, which were returned to 27°C for 2 and 6 hours. Cold exposure (acutely and chronically) led to increases in BAT oxidative activity, which was accompanied by concomitant increases in glucose and NEFA uptake. The increases were particularly high in cold-adapted rats and largely readily reduced by the return to a warm environment. The cold-induced increase in oxidative activity was meaningfully blunted by nicotinic acid, a lipolysis inhibitor, which emphasizes in vivo the key role of intracellular lipid in BAT thermogenesis. The changes in BAT oxidative activity and glucose and NEFA uptakes were paralleled by inductions of genes involved in not only oxidative metabolism but also in energy substrate replenishment (triglyceride and glycogen synthesis). The capacity of BAT for energy substrate replenishment is remarkable.

β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

“…Overall, we show that cold exposure induced fat browning and activated mitochondrial function; these results are consistent with previous studies (23)(24)(25). Therefore, we also suggest that BLC shows comparable effects to cold stimulation on fat browning.…”

“…4D). Previous studies have shown that activated mitochondrial function can be induced by cold stress or b-adrenergic stimuli as well as by the expression of brown adipocyte-specific genes (23)(24)(25). Exposure of mice to cold temperatures in this study resulted in an ;15-fold increase in UCP1 mRNA levels and a significant increase in UCP1 protein levels in the scWAT of mice compared with mice at room temperature ( Supplementary Fig.…”

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

“…At the end of the 14 days of adaptation and before a 6-h fasting period (0600 -1200), mice were killed under isoflurane while blood was sampled in EDTA-coated tubes through intracardiac puncture 1 h following the CL injection. Plasma glucose, nonesterified fatty acid (NEFA), and triglyceride levels were measured as described previously (19), and insulin was measured by an ultrasensitive mouse insulin ELISA kit (no. 90080; Crystal Chem, Downers Grove, IL).…”

“…Chemical detection of the PCR products was achieved with SYBR Green (172-5271; Bio-Rad) on the CFX384 touch real-time PCR system (Bio-Rad, Mississauga, ON, Canada). Specificity of amplification was ensured using melt curve analyses followed by agarose gel electrophoresis of the amplified products, as described previously (19). Fold differences in target mRNA expression were calculated using the 2-delta cycle threshold method and ␤-microglobulin as the housekeeping gene.…”

“…For [ 11 C]acetate images, dynamic series of 28 frames (1 ϫ 30, 12 ϫ 10, 8 ϫ 30, 6 ϫ 90, and 1 ϫ 300 s) were sorted out, whereas 30 frames (1 ϫ 30, 12 ϫ 10, 8 ϫ 30, 6 ϫ 90, and 3 ϫ 300 s) were used for 18 FDG and 18 FTHA imaging, and threedimensional images were reconstructed using 15 iterations of a maximum-likelihood expectation-maximization algorithm incorporating physical description of the detector response function. Regions of interest (ROIs) were drawn on short-axis images and confirmed with the CT scan (19). Time-activity curves were quantified in matching ROIs of […”