Fatty Acids Rescue the Thermogenic Function of Sympathetically Denervated Brown Fat.
Fatty Acids Rescue the Thermogenic Function of Sympathetically Denervated Brown Fat.
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DOI：
10.3390/biom11101428
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发表时间：
2021-09-29
期刊：
影响因子：
5.5
通讯作者：
Xue B
中科院分区：
文献类型：
--
作者：
Cao Q;Wang S;Wang H;Cui X;Jing J;Yu L;Shi H;Xue B
交感神经系统（SNS）对棕色脂肪组织（BAT）的神经支配被认为是棕色脂肪产热的动力。然而，我们惊讶地发现，BAT SNS神经支配不利于小鼠在长时间的冷暴露期间保持适当的体温。在这里，我们的目的是揭示在BAT神经支配的情况下维持棕色脂肪产热的生理因素。在冷暴露期间体温最初下降后，在肩胛间BAT中进行SNS手术去神经的小鼠逐渐恢复其与假手术小鼠相当的温度。手术去神经的BAT也保持相当大的解偶联蛋白1（UCP 1）蛋白沿着基础去甲肾上腺素（NE）在一个类似的水平，假手术对照，这与增加循环NE。此外，去神经支配的小鼠表现出循环中游离脂肪酸水平增加。事实上，手术切除脂肪细胞中CGI-58缺失的小鼠神经，一种缺乏从WAT释放脂肪酸的脂解能力的模型，显著降低了BAT UCP 1蛋白，并使小鼠对寒冷敏感。我们的结论是，循环脂肪酸和NE可能是维持BAT的产热功能和体温的BAT交感神经支配的情况下的关键因素。
Sympathetic nervous system (SNS) innervation into brown adipose tissue (BAT) has been viewed as an impetus for brown fat thermogenesis. However, we surprisingly discovered that BAT SNS innervation is dispensable for mice to maintain proper body temperature during a prolonged cold exposure. Here we aimed to uncover the physiological factors compensating for maintaining brown fat thermogenesis in the absence of BAT innervation. After an initial decline of body temperature during cold exposure, mice with SNS surgical denervation in interscapular BAT gradually recovered their temperature comparable to that of sham-operated mice. The surgically denervated BAT also maintained a sizable uncoupling protein 1 (UCP1) protein along with basal norepinephrine (NE) at a similar level to that of sham controls, which were associated with increased circulating NE. Furthermore, the denervated mice exhibited increased free fatty acid levels in circulation. Indeed, surgical denervation of mice with CGI-58 deletion in adipocytes, a model lacking lipolytic capacity to release fatty acids from WAT, dramatically reduced BAT UCP1 protein and rendered the mice susceptible to cold. We conclude that circulating fatty acids and NE may serve as key factors for maintaining BAT thermogenic function and body temperature in the absence of BAT sympathetic innervation.
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影响因子：
64.8
作者：
Nguyen, Khoa D.;Qiu, Yifu;Cui, Xiaojin;Goh, Y. P. Sharon;Mwangi, Julia;David, Tovo;Mukundan, Lata;Brombacher, Frank;Locksley, Richard M.;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
82.9
作者：
Fischer K;Ruiz HH;Jhun K;Finan B;Oberlin DJ;van der Heide V;Kalinovich AV;Petrovic N;Wolf Y;Clemmensen C;Shin AC;Divanovic S;Brombacher F;Glasmacher E;Keipert S;Jastroch M;Nagler J;Schramm KW;Medrikova D;Collden G;Woods SC;Herzig S;Homann D;Jung S;Nedergaard J;Cannon B;Tschöp MH;Müller TD;Buettner C
通讯作者：
Buettner C
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
2.5
作者：
Cui X;Nguyen NL;Zarebidaki E;Cao Q;Li F;Zha L;Bartness T;Shi H;Xue B
通讯作者：
Xue B
影响因子：
5.8
作者：
Ghorbani, M;Claus, TH;HimmsHagen, J
通讯作者：
HimmsHagen, J