Zheng Fenping, Kim Yonwook J, Moran Timothy H, Li Hong, Bi Sheng
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Department of Endocrinology, The Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Sci Rep. 2016 Apr 7;6:24238. doi: 10.1038/srep24238.
Transthyretin (TTR) is a blood and cerebrospinal fluid transporter of thyroxine and retinol. Gene expression profiling revealed an elevation of Ttr expression in the dorsomedial hypothalamus (DMH) of rats with exercise-induced anorexia, implying that central TTR may also play a functional role in modulating food intake and energy balance. To test this hypothesis, we have examined the effects of brain TTR on food intake and body weight and have further determined hypothalamic signaling that may underlie its feeding effect in rats. We found that intracerebroventricular (icv) administration of TTR in normal growing rats decreased food intake and body weight. This effect was not due to sickness as icv TTR did not cause a conditioned taste aversion. ICV TTR decreased neuropeptide Y (NPY) levels in the DMH and the paraventricular nucleus (P < 0.05). Chronic icv infusion of TTR in Otsuka Long-Evans Tokushima Fatty rats reversed hyperphagia and obesity and reduced DMH NPY levels. Overall, these results demonstrate a previously unknown anorectic action of central TTR in the control of energy balance, providing a potential novel target for treating obesity and its comorbidities.
甲状腺素运载蛋白（TTR）是甲状腺素和视黄醇的血液及脑脊液转运蛋白。基因表达谱分析显示，运动诱导性厌食大鼠的背内侧下丘脑（DMH）中Ttr表达升高，这意味着中枢TTR可能在调节食物摄入和能量平衡中也发挥功能性作用。为了验证这一假设，我们研究了脑内TTR对食物摄入和体重的影响，并进一步确定了可能是其在大鼠中产生摄食效应基础的下丘脑信号传导。我们发现，向正常生长的大鼠脑室内（icv）注射TTR会降低食物摄入量和体重。这种效应并非由疾病引起，因为脑室内注射TTR并未导致条件性味觉厌恶。脑室内注射TTR降低了DMH和室旁核中神经肽Y（NPY）的水平（P < 0.05）。在大冢长-伊万里德岛肥胖大鼠中慢性脑室内输注TTR可逆转食欲亢进和肥胖，并降低DMH中NPY的水平。总体而言，这些结果证明了中枢TTR在能量平衡控制中一种此前未知的厌食作用，为治疗肥胖及其合并症提供了一个潜在的新靶点。
