Ahmad Muhammad, Wu Shang, Luo Shengyao, Shi Wenjia, Guo Xuan, Cao Yuansheng, Perrimon Norbert, He Li
Department of Genetics, Harvard Medical School, Boston, MA, USA.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Nat Commun. 2025 Jan 2;16(1):247. doi: 10.1038/s41467-024-55371-y.
Propagation of intercellular calcium waves through tissues has been found to coordinate different multicellular responses. Nevertheless, our understanding of how calcium waves operate remains limited. In this study, we explore the real-time dynamics of intercellular calcium waves in Drosophila adipose tissues. We identify Adipokinetic Hormone (AKH), the fly functional homolog of glucagon, as the key factor driving Ca activities in adipose tissue. We find that AKH, which is released into the hemolymph from the AKH-producing neurosecretory cells, stimulates calcium waves in the larval fat by a previously unrecognized gap-junction-independent mechanism to promote lipolysis. In the adult fat body, however, gap-junction-dependent intercellular calcium waves are triggered by a presumably uniformly diffused AKH. Additionally, we discover that amino acids activate the AKH-producing neurosecretory cells, leading to increased intracellular Ca and AKH secretion. Altogether, we show that dietary amino acids regulate the AKH release from the AKH-producing neurosecretory cells in the brain, which subsequently stimulates gap-junction-independent intercellular calcium waves in adipose tissue, enhancing lipid metabolism.
已发现细胞间钙波在组织中的传播可协调不同的多细胞反应。然而，我们对钙波如何发挥作用的理解仍然有限。在这项研究中，我们探索了果蝇脂肪组织中细胞间钙波的实时动态。我们确定脂肪动激素（AKH），即胰高血糖素在果蝇中的功能同源物，是驱动脂肪组织中钙活动的关键因素。我们发现，从产生AKH的神经分泌细胞释放到血淋巴中的AKH，通过一种以前未被认识的不依赖间隙连接的机制刺激幼虫脂肪中的钙波，以促进脂肪分解。然而，在成年脂肪体中，依赖间隙连接的细胞间钙波是由可能均匀扩散的AKH触发的。此外，我们发现氨基酸可激活产生AKH的神经分泌细胞，导致细胞内钙增加和AKH分泌。总之，我们表明饮食中的氨基酸调节大脑中产生AKH的神经分泌细胞释放AKH，随后刺激脂肪组织中不依赖间隙连接的细胞间钙波，增强脂质代谢。
