Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Center for NanoImaging, Brigham and Women's Hospital, Cambridge, Massachusetts, USA.
JCI Insight. 2017 Mar 9;2(5):e90349. doi: 10.1172/jci.insight.90349.
Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging.
稳定同位素示踪剂的定量分析揭示了活体组织的动态状态。一种新形式的成像质谱分析能够在比立方微米还小的区域内定量同位素比值，使我们称之为多同位素成像质谱分析的方法能够以单细胞水平测量稳定同位素示踪剂的细胞更新和代谢。在首例人体研究中，我们利用 DNA 合成和从头脂肪生成的稳定同位素示踪剂来前瞻性地测量细胞生成和脂肪细胞脂质更新。在一项健康成年人的研究中，我们阐明了新脂肪细胞生成和脂肪细胞脂质更新随年龄的下降。线性回归模型表明，衰老效应可能是由胰岛素样生长因子-1（IGF-1）的下降所介导的。因此，这项研究建立了一种在亚细胞分辨率下测量人体细胞更新和代谢的方法，同时暗示了生长激素/IGF-1 轴在脂肪组织衰老中的作用。
