Spatiotemporal Heterogeneity of De Novo Lipogenesis in Fixed and Living Single Cells

脂肪生成 脂滴 脂质代谢 脂肪细胞 化学 生物物理学 细胞 生物 生物化学 内科学 内分泌学 脂肪组织 医学
作者
Sydney O. Shuster,Michael J. Burke,Caitlin M. Davis
出处
期刊:Journal of Physical Chemistry B [American Chemical Society]
卷期号:127 (13): 2918-2926 被引量:14
标识
DOI:10.1021/acs.jpcb.2c08812
摘要

De novo lipogenesis (DNL) is a critical metabolic process that provides the majority of lipids for adipocyte and liver tissue. In cancer, obesity, type II diabetes, and nonalcoholic fatty liver disease DNL becomes dysregulated. A deeper understanding of the rates and of subcellular organization of DNL is necessary for identifying how this dysregulation occurs and varies across individuals and diseases. However, DNL is difficult to study inside the cell because labeling lipids and their precursors is not trivial. Existing techniques either can only measure parts of DNL, like glucose uptake, or do not provide spatiotemporal resolution. Here, we track DNL in space and time as isotopically labeled glucose is converted to lipids in adipocytes using optical photothermal infrared microscopy (OPTIR). OPTIR provides submicron resolution infrared imaging of the glucose metabolism in both living and fixed cells while also reporting on the identity of lipids and other biomolecules. We show significant incorporation of the labeled carbons into triglycerides in lipid droplets over the course of 72 h. Live cells had better preservation of lipid droplet morphology, but both showed similar DNL rates. Rates of DNL, as measured by the ratio of 13C-labeled lipid to 12C-labeled lipid, were heterogeneous, with differences within and between lipid droplets and from cell to cell. The high rates of DNL measured in adipocyte cells match upregulated rates of DNL previously reported in PANC1 pancreatic cancer cells. Taken together, our findings support a model where DNL is locally regulated to meet energy needs within cells.
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