Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features.
Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features.
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DOI：
10.1080/21623945.2020.1827519
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发表时间：
2020-12
期刊：
影响因子：
3.3
通讯作者：
Holm C
中科院分区：
文献类型：
--
作者：
Axling U;Cavalera M;Degerman E;Gåfvels M;Eggertsen G;Holm C
本研究的目的是阐明胆汁酸发挥有益代谢作用的机制，使用Cyp 8b 1 −/-小鼠作为模型。这些小鼠不能合成胆酸，导致鹅去氧胆酸合成增加和胆汁酸池扩大。Cyp 8b 1 −/-小鼠被发现可以防止高脂肪饮食诱导的肥胖。弹式量热法测量显示Cyp 8b 1 −/小鼠的粪便能量输出增加。间接量热法测量表明Cyp 8b 1 −/-小鼠的能量消耗增加。膳食耐受性测试显示葡萄糖处理没有差异，但Cyp 8b 1 −/-小鼠的胰岛素反应较低。静脉内葡萄糖耐量测试以及离体胰岛的静态孵育显示，两组之间没有差异，而胰岛素耐量测试显示，Cyp 8b 1-/-小鼠的胰岛素敏感性有所改善。编码线粒体转录因子A（TFAM）和2型-碘甲腺原氨酸脱碘酶的基因在Cyp 8b 1/-小鼠的棕色脂肪组织中上调，Western印迹分析显示TFAM丰度增加，UCP 1丰度增加的趋势。TFAM和UCP 1的上调伴随着线粒体密度的增加，如透射电子显微镜所示。Cyp 8b 1 −/-小鼠的白色脂肪细胞在脂解实验中表现出对儿茶酚胺和胰岛素的反应性增加，并增加胰岛素刺激的脂肪生成。总之，增加的能量消耗，棕色脂肪细胞的线粒体密度和粪便能量输出都可能有助于保护Cyp 8b 1 −/-小鼠免受饮食诱导的肥胖。Cyp 8b 1 −/-小鼠的胰岛素敏感性增强伴随着白色脂肪细胞的激素反应性增加。
The aim of this study was to elucidate mechanisms whereby bile acids exert beneficial metabolic effects, using the Cyp8b1−/- mouse as model. These mice are unable to synthesize cholic acid, resulting in increased synthesis of chenodeoxycholic acid and enlarged bile acid pool. Cyp8b1−/- mice were found to be protected against high-fat diet induced obesity. Bomb calorimetry measurements showed increased faecal energy output in Cyp8b1−/mice. Indirect calorimetry measurements demonstrated increased energy expenditure in Cyp8b1−/- mice. Meal tolerance tests revealed no differences in glucose disposal, but the insulin response was lower in Cyp8b1−/- mice. Intravenous glucose tolerance tests, as well as static incubations of isolated islets, showed no difference between the groups, whereas insulin tolerance tests demonstrated improved insulin sensitivity in Cyp8b1−/- mice. The genes encoding mitochondrial transcription factor A (TFAM) and type 2-iodothyronine deiodinase were upregulated in brown adipose tissue of Cyp8b1/- mice and Western blot analyses showed increased abundance of TFAM, and a trend towards increased abundance of UCP1. The upregulation of TFAM and UCP1 was accompanied by increased mitochondrial density, as shown by transmission electron microscopy. White adipocytes of Cyp8b1−/- mice exhibited increased responsiveness to both catecholamines and insulin in lipolysis experiments and increased insulin-stimulated lipogenesis. In conclusion, increased energy expenditure, mitochondrial density of brown adipocytes and faecal energy output may all contribute to the protection against diet-induced obesity of Cyp8b1−/- mice. Enhanced insulin sensitivity of Cyp8b1−/- mice is accompanied by increased hormonal responsiveness of white adipocytes.
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DOI：
10.1152/ajpendo.00470.2002
发表时间：
2003-09-01
影响因子：
5.1
作者：
Brommage, R
通讯作者：
Brommage, R
影响因子：
64.8
作者：
Watanabe, M;Houten, SM;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
4.8
作者：
Watanabe, Mitsuhiro;Horai, Yasushi;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
9.8
作者：
Ahren, B;Simonsson, E;Sundler, F
通讯作者：
Sundler, F
影响因子：
2.2
作者：
MOODY, AJ;STAN, MA;GLIEMANN, J
通讯作者：
GLIEMANN, J