Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress.
Epididymal Fat-Derived Sympathoexcitatory Signals Exacerbate Neurogenic Hypertension in Obese Male Mice Exposed to Early Life Stress.
复制标题
附睾脂肪源性交感神经兴奋信号加重早期生活应激的肥胖雄性小鼠的神经源性高血压。
DOI：
10.1161/hypertensionaha.121.17298
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Loria AS
中科院分区：
文献类型：
--
作者：
Dalmasso C;Leachman JR;Ghuneim S;Ahmed N;Schneider ER;Thibault O;Osborn JL;Loria AS
补充数字内容可在正文中找到。此前，我们已经表明，暴露于母体分离和早期断奶(MSEW)的雄性小鼠-早期生活应激的小鼠模型-在喂食高脂肪饮食时，与对照组相比，平均动脉压升高。由于脂肪对感觉神经的刺激已被证明可以触发脂肪传入反射，我们测试了MSEW雄性小鼠是否通过这种交感兴奋机制的过度激活而表现出肥胖相关的高血压。在高脂饮食16周后，与对照组相比，MSEW小鼠表现出更高的血压、交感神经激活和对α肾上腺素能阻滞剂更强的降压反应(P<；0.05；n=8)，尽管肥胖和血浆瘦素没有差异。在附睾白脂肪组织中急性注射辣椒素(1.5pmoL/μL，8μL/个部位，4个部位，双侧)可增加MSEW小鼠的总升压反应(110±19vs284±33 mm Hg×30分钟；P<；0.05；n=8)。这种反应与OVLT、下丘脑室旁后核和RVLm的神经元激活有关(P<；0.05与对照组；n=6-7)。去肾神经治疗消除了肥胖MSEW小鼠的急性和慢性平均动脉压升高。此外，使用树脂毒素(10pmol/µL溶液；n=6)选择性去感觉神经切断附睾白脂肪组织，只降低肥胖MSEW小鼠的平均动脉压(P<；0.05与对照组相比)。肥胖的MSEW小鼠附睾白色脂肪组织中色氨酸羟化酶(TPH1)的mRNA表达及其合成产物5-羟色胺水平均升高(8.3±1.9对16.6±1.7微克/毫克组织；P<；0.05与对照组相比)。因此，来自附睾白色脂肪组织的传入感觉信号可能有助于肥胖雄性小鼠在早期生活应激下表现出的脂肪-脑-血压轴的恶化。
Supplemental Digital Content is available in the text. Previously, we have shown that male mice exposed to maternal separation and early weaning (MSEW)—a mouse model of early life stress—display increased mean arterial pressure compared with controls when fed a high-fat diet. As the stimulation of sensory nerves from fat has been shown to trigger the adipose afferent reflex, we tested whether MSEW male mice show obesity-associated hypertension via the hyperactivation of this sympathoexcitatory mechanism. After 16 weeks on high-fat diet, MSEW mice displayed increased blood pressure, sympathetic activation, and greater depressor response to an α-adrenergic blocker when compared with controls (P<0.05; n=8), despite no differences in adiposity and plasma leptin. The acute infusion of capsaicin in epididymal white adipose tissue (1.5 pmol/μL of capsaicin, 8 μL/per site, 4 sites, bilaterally) increased the total pressor response in MSEW mice compared with controls (110±19 versus 284±33 mm Hg×30 minutes; P<0.05; n=8). This response was associated with neuronal activation in OVLT, posterior paraventricular nucleus of the hypothalamus, and RVLM (P<0.05 versus control; n=6–7). Renal denervation abolished both the acute and chronic elevated mean arterial pressure in obese MSEW mice. Moreover, selective sensory denervation of epididymal white adipose tissue using resiniferatoxin (10 pmol/µL solution; n=6) decreased mean arterial pressure in obese MSEW mice only (P<0.05 versus control). Obese MSEW mice displayed increased epididymal white adipose tissue levels of both tryptophan hydroxylase (Tph1) mRNA expression and its synthesis product serotonin (8.3±1.9 versus 16.6±1.7 ug/mg tissue; P<0.05 versus control). Thus, afferent sensory signals from epididymal white adipose tissue may contribute to the exacerbated fat–brain–blood pressure axis displayed by obese male mice exposed to early life stress.