Braun Jessica L, Geromella Mia S, Hamstra Sophie I, Fajardo Val A
Department of Kinesiology Brock University St. Catharines ON USA.
Centre for Bone and Muscle Health Brock University St. Catharines ON USA.
FASEB Bioadv. 2020 Sep 2;2(10):579-586. doi: 10.1096/fba.2020-00052. eCollection 2020 Oct.
Neuronatin (NNAT) was originally discovered in 1995 and labeled as a brain developmental gene due to its abundant expression in developing brains. Over the past 25 years, researchers have uncovered NNAT in other tissues; notably, the hypothalamus, pancreatic β-cells, and adipocytes. Recent evidence in these tissues indicates that NNAT plays a significant role in metabolism whereby it regulates food intake, insulin secretion, and adipocyte differentiation. Furthermore, genetic deletion of in mice lowers whole-body energy expenditure and increases susceptibility to diet-induced obesity and glucose intolerance; however, the underlying cellular mechanisms remain unknown. Based on its sequence homology with phospholamban, NNAT has a purported role in regulating the sarco(endo)plasmic reticulum Ca ATPase (SERCA) pump. However, NNAT also shares sequence homology with sarcolipin, which has the unique property of uncoupling the SERCA pump, increasing whole-body energy expenditure and thus promoting adaptive thermogenesis in states of caloric excess or cold exposure. Thus, in this article, we discuss the accumulating evidence suggestive of NNAT's role in whole-body metabolic regulation, while highlighting its potential to mediate adaptive thermogenesis via SERCA uncoupling.
神经调节素（NNAT）最初于1995年被发现，因其在发育中的大脑中大量表达而被标记为一种脑发育基因。在过去的25年里，研究人员在其他组织中也发现了NNAT；特别是下丘脑、胰腺β细胞和脂肪细胞。这些组织中的最新证据表明，NNAT在新陈代谢中起着重要作用，它调节食物摄入、胰岛素分泌和脂肪细胞分化。此外，小鼠体内NNAT的基因缺失会降低全身能量消耗，并增加对饮食诱导的肥胖和葡萄糖不耐受的易感性；然而，其潜在的细胞机制仍然未知。基于其与受磷蛋白的序列同源性，NNAT据称在调节肌浆（内质）网Ca ATP酶（SERCA）泵方面发挥作用。然而，NNAT也与肌脂蛋白具有序列同源性，肌脂蛋白具有使SERCA泵解偶联的独特特性，可增加全身能量消耗，从而在热量过剩或冷暴露状态下促进适应性产热。因此，在本文中，我们讨论了越来越多的证据表明NNAT在全身代谢调节中的作用，同时强调了其通过SERCA解偶联介导适应性产热的潜力。
