Dissociation Between Brown Adipose Tissue ¹⁸F-FDG Uptake and Thermogenesis in Uncoupling Protein 1–Deficient Mice

Abstract

18 F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18 F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective b3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18 F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy-3 H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18 F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3 H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18 F-FDG uptake independently of UCP1 thermogenic function.

β 3 -Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: Mediation through the mTOR pathway

“…In this respect, the present studies are also an in vivo extension of earlier studies showing that UCP1 is not a prerequisite for adrenergically induced glucose uptake in cultured brown adipocytes [46] or in intact mice [47]. In contrast, Inokuma et al.…”

CPEB 2‐dependent translation of long 3′‐ UTR Ucp1 mRNA promotes thermogenesis in brown adipose tissue

“…Although a previous study claimed that norepinephrine‐stimulated uptake of 2‐deoxy‐ 3 H‐glucose is impaired in UCP1‐KO BAT (Inokuma et al , ), a recent report showed that UCP1‐KO mice with reduced BAT temperature and oxygen consumption exhibited normal BAT uptake of 18 F‐FDG in response to CL316243 treatment. Moreover, glycolytic flux and 2‐deoxy‐ 3 H‐glucose uptake in isolated UCP1‐KO brown adipocytes were not affected despite defective uncoupled respiration (Hankir et al , ). Adrenergic stimulation by CL316243 (Hankir et al , ) or by cold exposure (Fig EV3B) appears to increase BAT 18 F‐FDG uptake independent of UCP1.…”

“…Moreover, glycolytic flux and 2‐deoxy‐ 3 H‐glucose uptake in isolated UCP1‐KO brown adipocytes were not affected despite defective uncoupled respiration (Hankir et al , ). Adrenergic stimulation by CL316243 (Hankir et al , ) or by cold exposure (Fig EV3B) appears to increase BAT 18 F‐FDG uptake independent of UCP1. The loss of CPEB2‐promoted Ucp1L translation does not account for decreased 18 FDG uptake in CPEB2‐KO BAT (Fig EV3A).…”

Assessment of the aging of the brown adipose tissue by18F-FDG PET/CT imaging in the progeria mouse model LmnaG609G/G609G

“…In the cold stimulation, β 3-AR not only increases glucose transport, but also increases UCP1 expression and activity (Collins et al 2010). Although Hankir MK et al thought that BAT 18 F-FDG uptake and UCP1-mediated heat production can be dissociated (Hankir et al 2017), most studies suggest that UCP1 is necessary for norepinephrine-induced glucose utilization in BAT (Inokuma et al 2005b). The reduction in expression of UCP1 in Lmna G609G/G609G mice further reduced the uptake of 18 F-FDG in BAT.…”