Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, California 95616, USA; Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul 08826, South Korea.
Division of Endocrinology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, California 95616, USA.
J Cyst Fibros. 2023 Jan;22(1):132-139. doi: 10.1016/j.jcf.2022.08.012. Epub 2022 Sep 8.
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 (CFTR).
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 CFTR mice.
Our data reveal a new role for CFTR in the regulation of adipocyte thermogenesis.
囊性纤维化（CF）的特征是生长和体重降低，这是多因素的。CF 小鼠模型缺乏易导致能量负平衡的关键疾病特征，如肺部感染或外分泌胰腺功能不全，但它们仍然表现出生长缺陷和异常增加的能量消耗。脂肪细胞产热是否有助于 CF 小鼠静息能量消耗增加尚不清楚。
我们检查了 CFTR 在产热棕色脂肪组织（BAT）中的表达，并使用 BAT 特异性 CFTR 缺失小鼠（CFTR）研究了 CFTR 的功能作用。
CFTR 蛋白在小鼠 BAT 中的表达水平与肺部相当。在小鼠中 BAT 特异性缺失 CFTR 会增加全身能量消耗，这与冷暴露时交感神经刺激有关。这些小鼠在高脂肪饮食上的体重增加受到抑制。然而，CFTR 缺陷的棕色脂肪细胞本身的产热反应受损，而不是增强。这些细胞表现出脂肪分解减少，对肾上腺素刺激的 cAMP/PKA 信号通路的激活减弱。这表明其他组织中代偿性产热可能解释了 CFTR 小鼠中观察到的全身性能量消耗增加。
我们的数据揭示了 CFTR 在调节脂肪细胞产热中的新作用。
