Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue,Molecular and Cellular Endocrinology

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Characterization of endogenous bile acid composition in individuals with cold-activated brown adipose tissue
Molecular and Cellular Endocrinology ( IF 4.1 ) Pub Date : 2021-07-28 , DOI: 10.1016/j.mce.2021.111403
Carsten T Herz ₁ , Oana C Kulterer ₂ , Marlene Prager ₃ , Felix B Langer ₄ , Gerhard Prager ₄ , Rodrig Marculescu ₅ , Günter Fauler ₆ , Marcus Hacker ₇ , Alexandra Kautzky-Willer ₃ , Michael Trauner ₈ , Alexander R Haug ₉ , Florian W Kiefer ₃

Affiliation

Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
Division of Medical-Chemical Laboratory Diagnostics, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria.

Introduction

Bile acid signaling has been suggested to promote BAT activity in various experimental models. However, little is known if and how physiologic bile acid metabolism is linked to BAT function in humans. Here we investigated the association between BAT activity and circulating bile acid concentrations in lean and obese individuals.

Methods

BAT ¹⁸F-fluorodeoxyglucose uptake was measured after a standardized cooling protocol by positron emission tomography/computed tomography. Cold-induced thermogenesis was assessed by indirect calorimetry. Fasting bile acid concentrations were determined by high performance liquid chromatography–high-resolution mass spectrometry.

Results

In a cohort of 24 BAT-negative and 20 BAT-positive individuals matched by age, sex, and body mass index, circulating bile acid levels were similar between groups except for higher ursodeoxycholic acid and a trend towards a lower 12α-OH/non-12α-OH bile acid ratio in lean participants with active BAT compared to those without. Moreover, the 12α-OH/non-12α-OH ratio, a marker of CYP8B1 activity, correlated negatively with BAT volume and activity.

Conclusion

Fasting concentrations of major bile acids are not associated with cold-induced BAT activity in humans. However, the inverse association between BAT activity and 12α-OH/non-12α-OH ratio may suggest CYP8B1 as a potential new target in BAT function and warrants additional investigation.

中文翻译：

冷激活棕色脂肪组织个体内源性胆汁酸成分的表征

介绍

已经提出胆汁酸信号传导在各种实验模型中促进 BAT 活性。然而，人们对生理性胆汁酸代谢是否以及如何与人类的 BAT 功能相关知之甚少。在这里，我们研究了瘦和肥胖个体的 BAT 活性与循环胆汁酸浓度之间的关联。

方法

在标准化冷却方案后，通过正电子发射断层扫描/计算机断层扫描测量BAT ¹⁸ F-氟脱氧葡萄糖摄取。通过间接量热法评估冷诱导的产热。通过高效液相色谱-高分辨率质谱法测定空腹胆汁酸浓度。

结果

在由年龄、性别和体重指数匹配的 24 名 BAT 阴性和 20 名 BAT 阳性个体组成的队列中，各组之间的循环胆汁酸水平相似，除了熊去氧胆酸较高和 12α-OH/非-与没有活跃 BAT 的人相比，活跃 BAT 的瘦参与者的 12α-OH 胆汁酸比率。此外，CYP8B1 活性标志物 12α-OH/非 12α-OH 比率与 BAT 体积和活性呈负相关。