Language：English   Publisher：International Journal of Obesity  

Background: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the β-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 β-ARs and BAT activity in human adults. Methods: Single nucleotide polymorphisms (SNPs) in β1-, β2-, and β3-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 β2-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. (Figure presented.)

DOI： 10.1038/s41366-024-01522-6

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Language：English   Publisher：Scientific Reports  

When lowlanders are exposed to environments inducing hypobaric hypoxia (HH) such as high mountains, hemodynamic changes occur to maintain oxygen levels in the body. However, changes to other physiological functions under such conditions have yet to be clarified. This study investigated changes in endocrine, inflammatory and immune parameters and individual differences during acute HH exposure using a climatic chamber (75 min of exposure to conditions mimicking 3500 m) in healthy lowlanders. Aldosterone and cortisol were significantly decreased and interleukin (IL)-6, IL-8 and white blood cell (WBC) counts were significantly increased after HH. Lower peripheral oxygen saturation (SpO2) was associated with higher IL-6 and WBC counts, and higher IL-8 was associated with higher cortisol. These findings suggest that endocrine, inflammatory and immune responses are evoked even with a short 75-min exposure to HH and individuals with lower SpO2 seemed to show more pronounced responses. Our results provide basic data for understanding the physiological responses and interactions of homeostatic systems during acute HH.

DOI： 10.1038/s41598-023-39894-w

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Language：English   Publisher：長崎大学医学部  

地域在住成人におけるFTO遺伝子型と肥満および骨健康との関連性を横断的前向き観察研究で評価した。五島列島在住者1828名(男性650名、女性1178名)を対象に、脂肪量および肥満関連FTO遺伝子の遺伝子型と骨量減少との関連性を検討した。踵骨量は定量的超音波検査(QUS)で評価し、一塩基多型(SNP)rs1421085は加水分解プローブを用いて遺伝子型を決定した。被験者の年齢中央値は男性69歳、女性68歳であった。各遺伝子型のBMI中央値はCC型24.3、CT型23.0、TT型22.6で遺伝子型間に差がみられたが、骨量中央値には差はなかった。マイナーアレルと過体重間には遺伝子量依存的に有意な関連が認められた。ロジスティック回帰分析では、65歳～75歳のマイナーアレル男性保因者においては年齢およびBMI調整後のQUS Tスコアが-2.0未満の低骨量に対する有意な保護的関連がみられたが、女性ではみられなかった。FTO遺伝子多型が骨健康に関与する可能性が示された。

Language：Japanese