Intracellular glycolysis in brown adipose tissue is essential for optogenetically induced nonshivering thermogenesis in mice.
Intracellular glycolysis in brown adipose tissue is essential for optogenetically induced nonshivering thermogenesis in mice.
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DOI：
10.1038/s41598-018-25265-3
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发表时间：
2018-04-27
影响因子：
4.6
通讯作者：
Jo YH
中科院分区：
文献类型：
--
作者：
Jeong JH;Chang JS;Jo YH
交感神经系统（SNS）激活后脂滴中脂肪酸的释放是棕色脂肪组织（BAT）非颤抖性产热的关键步骤。然而，细胞内脂解似乎不是冷诱导产热的关键。由于SNS的激活增加葡萄糖摄取，我们研究了细胞内糖酵解是否在BAT产热中起作用。为了在体内刺激BAT支配的交感神经，我们通过将酪氨酸羟化酶-Cre小鼠与停止的ChR 2小鼠杂交，在儿茶酚胺能纤维中表达通道视紫红质-2（ChR 2）。BAT的交感传出纤维的急性光遗传学刺激增加体温并降低血糖水平，其被β-肾上腺素能受体拮抗剂完全消除。BAT中Ucp 1基因的敲除阻断了光遗传学刺激对体温和葡萄糖摄取的影响。抑制BAT中的葡萄糖摄取和糖酵解消除了光遗传学诱导的产热。刺激交感神经可上调BAT中乳酸脱氢酶-A和-B基因的表达。光遗传刺激未能诱导产热处理后的LDH抑制剂。单羧酸转运蛋白1的药理学阻断和基因缺失完全消除了交感神经激活的作用。我们的研究结果表明，细胞内糖酵解和乳酸穿梭在调节BAT的急性产热中起着重要作用。
Release of fatty acids from lipid droplets upon activation of the sympathetic nervous system (SNS) is a key step in nonshivering thermogenesis in brown adipose tissue (BAT). However, intracellular lipolysis appears not to be critical for cold-induced thermogenesis. As activation of the SNS increases glucose uptake, we studied whether intracellular glycolysis plays a role in BAT thermogenesis. To stimulate BAT-innervating sympathetic nerves in vivo, we expressed channelrhodopsin-2 (ChR2) in catecholaminergic fibers by crossbreeding tyrosine hydroxylase-Cre mice with floxed-stop ChR2 mice. Acute optogenetic stimulation of sympathetic efferent fibers of BAT increased body temperature and lowered blood glucose levels that were completely abolished by the β-adrenergic receptor antagonist. Knockdown of the Ucp1 gene in BAT blocked the effects of optogenetic stimulation on body temperature and glucose uptake. Inhibition of glucose uptake in BAT and glycolysis abolished optogenetically induced thermogenesis. Stimulation of sympathetic nerves upregulated expression of the lactate dehydrogenase-A and -B genes in BAT. Optogenetic stimulation failed to induce thermogenesis following treatment with the LDH inhibitor. Pharmacological blockade and genetic deletion of the monocarboxylate transporter 1 completely abolished the effects of sympathetic activation. Our results suggest that intracellular glycolysis and lactate shuttle play an important role in regulating acute thermogenesis in BAT.
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影响因子：
--
作者：
MARETTE, A;BUKOWIECKI, LJ
通讯作者：
BUKOWIECKI, LJ
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
影响因子：
15.9
作者：
Guerra, C;Koza, RA;Kozak, LP
通讯作者：
Kozak, LP
DOI：
10.1111/j.1432-1033.1982.tb07060.x
发表时间：
1982-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
LOCKE, RM;RIAL, E;NICHOLLS, DG
通讯作者：
NICHOLLS, DG
影响因子：
11.1
作者：
Albert V;Svensson K;Shimobayashi M;Colombi M;Muñoz S;Jimenez V;Handschin C;Bosch F;Hall MN
通讯作者：
Hall MN