Abstract
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Objectives: Brown adipose tissue (BAT) is responsible for adaptive thermogenesis and energy expenditure, its activity is mediated by mitochondrial uncoupling protein 1 (UCP-1) which leads to the heat production by uncoupling electron transport chain. It is known that the genetic deficiency of RAGE (receptor for advanced glycation end products) can prevent the effects of high-fat diet (HFD) on energy expenditure, obesity, adipose tissue inflammation, and insulin resistance. Thus, the aim of this study was to compare the BAT activity in RAGE null and wild type (WT) mice in response to different diet conditions.
Methods: RAGE knock out (Ager-/-, RKO) and WT mice treated with low fat (LFD) and high fat diet (HFD) underwent [18F]FDG PET-CT imaging under identical mild cold-stimulated conditions (4 °C) for interscapular BAT (iBAT) quantification. Dynamic PET scans of all mice were performed for 60 min, followed by CT (6 min) for the purpose of attenuation correction and co-registration. All mice were fasted for at least 4 hrs and exposed to a cold-pack (4 °C) for 30 min before each scan and during the entire scan. The values for different parameters such as SUVmean (mean standard uptake values), SUVR (ratio of SUViBAT / SUVmuscle), and %ID/g for uptake in iBAT were determined.
Results: The uptake of [18F]FDG in the iBAT of WT mice fed HFD was significantly reduced by three folds as compared to that in WT mice fed LFD (SUVRWT-HFD = 1.40±0.07, SUVRWT-LFD = 4.03±0.38; P = 0.00003). In contrast, in RKO mice, BAT activity was not significantly affected by HFD as indicated by similar uptakes of [18F]FDG in iBAT between HFD (SUVRRKO-HFD: 1.52±0.13) and LFD (SUVRRKO-LFD: 2.14±0.10) of RKO mice (P = 0.3). Intergroup comparison showed that the uptake in iBAT in WT-LFD mice was almost double and significantly different from that in RKO-LFD (P = 0.007). However, under HFD intake, there was no significant difference in the iBAT uptakes between RKO-HFD and WT-HFD mice (P = 0.3). These results corroborate our previous findings on the measurement of mRNA transcripts for UCP-1 in the BAT of WT and RAGE null mice fed HFD vs. LFD.
Conclusion: Our findings suggest that RAGE may contribute to altered energy expenditure, and may provide a protective effect against HFD by Ager deletion (Ager -/-). Research Support: The work is supported by The Center for Advanced Imaging Innovation and Research (CAI2R, www.cai2r.net) at New York University School of Medicine is supported by NIH/NIBIB grant number P41 EB017183.