ABSTRACT
BACKGROUND: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the ß-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding ß-ARs and BAT activity in human adults. METHODS: Single nucleotide polymorphisms (SNPs) in ß1-, ß2-, and ß3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIRTRS) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber. RESULTS: We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIRTRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits. CONCLUSIONS: The present study supports the importance of ß2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function.
Subject(s)
Adipose Tissue, Brown , Polymorphism, Single Nucleotide , Receptors, Adrenergic, beta-2 , Thermogenesis , Humans , Thermogenesis/physiology , Thermogenesis/genetics , Adipose Tissue, Brown/metabolism , Male , Adult , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/metabolism , Female , Middle Aged , Japan , Positron Emission Tomography Computed Tomography , Receptors, Adrenergic, beta-3/genetics , Receptors, Adrenergic, beta-3/metabolism , Asian People/geneticsABSTRACT
Oxygen uptake (VË O2) was measured during a non-exhaustive high-intensity intermittent cross-exercise (HIICE) protocol consisting of four alternating bouts of 20 âs running (R) and three bouts of bicycle exercise (BE) at â¼160% and â¼170% maximal oxygen uptake (VË O2max), respectively, with 10 âs between-bout rests (sequence R-BE-R-BE-R-BE-R). The VË O2 during the last BE ([52.2 â± â5.0] mL·kg-1·min-1) was significantly higher than the VË O2max of the BE ([48.0 â± â5.4] mL·kg-1·min-1, n â= â30) and similar to that of running. For clarifying the underlying mechanisms, a corresponding HIICE-protocol with BE and arm cranking ergometer exercise (AC) was used (sequence AC-AC-BE-AC-BE-AC-AC-BE). In some experiments, thigh blood flow was occluded by a cuff around the upper thigh. Without occlusion, the VË O2 during the AC ([39.2 â± â7.1] mL·kg-1·min-1 [6th bout]) was significantly higher than the VË O2max of AC ([30.2 â± â4.4] mL·kg-1·min-1, n â= â7). With occlusion, the corresponding VË O2 ([29.8 â± â3.9] mL·kg-1·min-1) was reduced to that of the VË O2max of AC and significantly less than the VË O2 without occlusion. These findings suggest that during the last bouts of HIICE may exceed the of the specific exercise, probably because it is a summation of the VË O2 for the ongoing exercise plus excess post-oxygen consumption (EPOC) produced by the previous exercise with a higher VË O2max.