Lung branching morphogenesis is accompanied by temporal metabolic changes towards a glycolytic preference

Area of Science:

• Developmental Biology
• Metabolic Biochemistry
• Cellular Respiration

Background:

• Lung branching morphogenesis involves complex epithelial-mesenchymal interactions.
• High proliferative rates during lung development require substantial energy and macromolecules.
• While molecular mechanisms are known, embryonic lung metabolic needs are understudied.

Purpose of the Study:

• To investigate the metabolic profile of early-stage chicken lung branching.
• To understand the metabolic requirements during embryonic lung development.

Main Methods:

• Ex vivo lung explant culture analyzed via 1H-NMR spectroscopy.
• Quantitative PCR (qPCR) to assess transcript levels of glycolytic enzymes and transporters.
• In situ hybridization, EdU assay, Western blot, and Clark-type electrode for proliferation, protein levels, and respiratory capacity.

Main Results:

• Progressive increase in alanine, lactate, and acetate production with decreasing glucose consumption during branching.
• Variations in glycolytic enzyme and transporter expression, with specific spatial patterns for LDHA and LDHB.
• High proliferation rates observed at active branching sites, with stable oxygen consumption.

Conclusions:

• Temporal metabolic shifts occur during early chicken lung branching morphogenesis.
• Embryonic chicken lungs exhibit a metabolic shift towards glycolysis and lactate production during branching.
• This metabolic rewiring is likely essential for successful lung development.