Sophia Pankoke, Lea Gerling, Matthias Ochs, Christian Mühlfeld, Julia Schipke
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引用次数: 0
Abstract
Pulmonary surfactant is essential for lung function and consists mainly of lipids, almost half of which in adult mammals originate from de novo synthesis in alveolar epithelial type-2 (AE2) cells. Obesogenic nutrition and hypoxia coexist in obese patients with chronic lung diseases. This study tested the hypothesis that diet-induced obesity and chronic hypoxia alter lipid metabolism and thereby deteriorate surfactant homeostasis. Male C57BL/6N mice were fed control diet (4% fat, 6% sucrose; CD), high-sucrose diet (4% fat, 46% sucrose; HSD) or high-fat diet (35% fat, 7% sucrose; HFD). After 27 weeks, half of each diet group was exposed to hypoxia (13% O2, Hyp) for 3 weeks. After 30 weeks, lung mechanics were assessed, and the blood, livers, and lungs were analyzed. In CD-fed mice, hypoxia induced lung mechanical changes indicative of reduced elastic recoil properties, as well as smaller lamellar bodies (LBs) and higher composite body volumes, suggesting an increased surfactant precursor formation. HSD and HFD induced lipid accumulation in liver and AE2 cells. In HSD-Hyp and HFD-Hyp, LB volumes per alveolar surface area were elevated, indicating compensatory increases in intracellular surfactant pools which were absent in CD-Hyp. Additionally, hypoxia-related lung mechanics alterations were less pronounced in HSD-Hyp and HFD-Hyp. Lung proteome analysis revealed that only a few lipid metabolism-associated proteins were similarly regulated within diet groups under hypoxia, with the most prominent changes in sucrose-fed hypoxic animals. Thus, individual diet-related metabolic states specifically affect the adaptation of the pulmonary lipid metabolism and intracellular surfactant assembly to chronic hypoxia.
期刊介绍:
The journal publishes regular articles and reviews in the areas of molecular, cell, and supracellular biology. In particular, the journal intends to provide a forum for publishing data that analyze the supracellular, integrative actions of gene products and their impact on the formation of tissue structure and function. Submission of papers with an emphasis on structure-function relationships as revealed by recombinant molecular technologies is especially encouraged. Areas of research with a long-standing tradition of publishing in Cell & Tissue Research include:
- neurobiology
- neuroendocrinology
- endocrinology
- reproductive biology
- skeletal and immune systems
- development
- stem cells
- muscle biology.