CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway.
CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway.
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DOI：
10.1016/j.jcf.2022.08.012
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发表时间：
2023-01
影响因子：
5.2
通讯作者：
Yoon, John C.
中科院分区：
文献类型：
--
作者：
Choi, Kyung-Mi;Cho, Sung-Hee;Kim, Jung Hak;Kim, Ae-Rhee Lilian;Kong, Xiangmudong;Yoon, John C.
囊性纤维化的特征是生长减慢和体重下降，这是多因素的。Cf小鼠模型缺乏易导致负能量平衡的关键疾病特征，如肺部感染或胰腺外分泌功能不全，但它们仍显示出生长缺陷和能量消耗异常增加。脂肪细胞产热是否导致CF小鼠静息能量消耗增加，目前尚不清楚。我们检测了CFTR在产热棕色脂肪组织(BAT)中的表达，并利用BAT特异性CFTR缺失小鼠(CFTRBATKO)研究了CFTR的功能作用。CFTR蛋白在小鼠蝙蝠中的表达水平与肺中的水平相当。在小鼠中，BAT特异性的CFTR失活增加了与冷暴露引起的交感神经刺激相关的全身能量消耗。在这些小鼠中，高脂肪饮食的体重增加是减弱的。然而，缺乏CFTR的棕色脂肪细胞本身损害了而不是增强了生热反应。这些细胞的特点是脂肪分解减少，cAMP/PKA信号通路在肾上腺素能刺激下被钝化激活。这表明，在CFTRBATKO小鼠中，其他组织的补偿性热产生可能是全身能量消耗增加的原因。我们的数据揭示了CFTR在脂肪细胞产热调节中的新作用。
Cystic fibrosis (CF) is characterized by reduced growth and lower body weight, which are multifactorial. CF mouse models lack key disease characteristics that predispose to a negative energy balance, such as pulmonary infections or exocrine pancreatic insufficiency, and yet they still exhibit a growth defect and an abnormally increased energy expenditure. Whether adipocyte thermogenesis contributes to the elevated resting energy expenditure in CF mice is unknown. We examined the expression of CFTR in thermogenic brown adipose tissue (BAT) and investigated a functional role for CFTR using BAT-specific CFTR null mice (CFTRBATKO). The CFTR protein is expressed in mouse BAT at levels comparable to those in the lungs. BAT-specific inactivation of CFTR in mice increases whole-body energy expenditure associated with sympathetic stimulation by cold exposure. Weight gain on a high-fat diet is attenuated in these mice. However, CFTR-deficient brown adipocytes themselves have impaired, rather than enhanced, thermogenic responses. These cells feature decreased lipolysis and blunted activation of the cAMP/PKA signaling pathway in response to adrenergic stimulation. This suggests that compensatory heat production in other tissues likely accounts for the increased systemic energy expenditure seen in CFTRBATKO mice. Our data reveal a new role for CFTR in the regulation of adipocyte thermogenesis.
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影响因子：
64.5
作者：
Chen Y;Zeng X;Huang X;Serag S;Woolf CJ;Spiegelman BM
通讯作者：
Spiegelman BM
DOI：
10.1186/1745-7580-4-5
发表时间：
2008-04-29
期刊：
Immunome research
影响因子：
--
作者：
Lattin JE;Schroder K;Su AI;Walker JR;Zhang J;Wiltshire T;Saijo K;Glass CK;Hume DA;Kellie S;Sweet MJ
通讯作者：
Sweet MJ
影响因子：
20.8
作者：
de Jong, Jasper M. A.;Sun, Wenfei;Petrovic, Natasa
通讯作者：
Petrovic, Natasa
影响因子：
5.1
作者：
FRIED, MD;DURIE, PR;PENCHARZ, PB
通讯作者：
PENCHARZ, PB
影响因子：
--
作者：
Jung SM;Sanchez-Gurmaches J;Guertin DA
通讯作者：
Guertin DA