Nguyen Ngoc Ly T, Barr Candace L, Ryu Vitaly, Cao Qiang, Xue Bingzhong, Bartness Timothy J
Department of Biology, Georgia State University, Atlanta, Georgia.
Center for Obesity Reversal, Georgia State University, Atlanta, Georgia; and.
Am J Physiol Regul Integr Comp Physiol. 2017 Jan 1;312(1):R132-R145. doi: 10.1152/ajpregu.00344.2016. Epub 2016 Nov 23.
White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16-24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30-40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.
白色脂肪组织(WAT)和棕色脂肪组织(BAT)受交感神经系统(SNS)支配和调节。然而,尚不清楚是否存在共同的或独立的中枢SNS传出通路至WAT和BAT来调节它们的功能。我们将两种携带独特荧光报告基因的伪狂犬病病毒同基因菌株(一种逆行跨神经元病毒示踪剂)注射到同一只西伯利亚仓鼠的肩胛间棕色脂肪组织(IBAT)和腹股沟白色脂肪组织(IWAT)中,以确定至二者的SNS通路。为了测试SNS对BAT和WAT协调控制的功能重要性,我们将IBAT去神经支配的仓鼠暴露于4°C环境16 - 24小时,并测量核心体温和脂肪温度以及脂肪组织中的去甲肾上腺素周转率(NETO)和解偶联蛋白1(UCP1)表达。总体而言,在整个神经轴上,支配IBAT的SNS神经元比IWAT更多。然而,中脑网状核中IWAT单标记神经元的百分比高于IBAT单标记神经元。后脑有30 - 40%的双标记神经元,而前脑有25%,这表明大脑中存在至BAT和WAT的共同SNS回路。中缝核是体温调节的关键区域,有~40%的双标记神经元。急性冷刺激期间,IBAT去神经支配的仓鼠能维持核心体温,且IWAT中米色脂肪细胞形成增加。与完整仓鼠相比,它们的IWAT的NETO、温度和UCP1表达也增加。这些数据为WAT和BAT的SNS相互作用在体温调节和米色脂肪细胞形成方面提供了有力的神经解剖学和功能证据。