Differential expression of lipid and carbohydrate metabolism genes in upper airway versus diaphragm muscle

Abstract

Study objectives: Contractile properties of upper airway muscles influence upper airway patency, an issue of particular importance for subjects with obstructive sleep apnea. Expression of genes related to cellular energetics is, in turn, critical for the maintenance of contractile integrity over time during repetitive activation. We tested the hypothesis that sternohyoid has lower expression of genes related to lipid and carbohydrate energetic pathways than the diaphragm.

Methods: Sternohyoid and diaphragm from normal adult rats were examined with gene expression arrays. Analysis focused on genes belonging to Gene Ontology (GO) groups carbohydrate metabolism and lipid metabolism.

Results: There were 433 genes with at least +/- 2-fold significant differential expression between sternohyoid and diaphragm, of which 192 had sternohyoid > diaphragm and 241 had diaphragm > sternohyoid expression. Among genes with higher sternohyoid expression, there was over-representation of the GO group carbohydrate metabolism (P = 0.0053, n = 13 genes, range of differential expression 2.1- to 6.2-fold) but not lipid metabolism (P = 0.44). Conversely, among genes with higher diaphragm expression, there was over-representation of the GO group lipid metabolism (P = 0.0000065, n = 32 genes, range of differential expression 2.0- to 37.9-fold) but not carbohydrate metabolism (P = 0.23). Nineteen genes with diaphragm > sternohyoid expression were related to fatty acid metabolism (P = 0.000000058), in particular fatty acid beta oxidation and biosynthesis in the mitochondria.

Conclusions: Sternohyoid has much lower gene expression than diaphragm for mitochondrial enzymes that participate in fatty acid oxidation and biosynthesis. This likely contributes to the lower fatigue resistance of pharyngeal upper airway muscles compared with the diaphragm.

Figure 1

Extent of differential expression between sternohyoid and diaphragm muscle of lipid metabolism genes. Left panel depicts data for 12 genes with higher expression in sternohyoid than diaphragm muscle; right panel depicts data for 32 genes with higher expression in diaphragm than sternohyoid muscle.

Figure 2

Genes with differential expression between sternohyoid and diaphragm muscle that are involved in specific steps of fatty acid β-oxidation. Genes with higher expression in sternohyoid than diaphragm are indicated in red; genes with higher expression in diaphragm than sternohyoid are indicated in green. Numbers indicate fold-differential expression.

Figure 3

Genes with differential expression between sternohyoid and diaphragm muscle that are involved in specific steps of fatty acid synthesis. Genes with higher expression in sternohyoid than diaphragm are indicated in red; genes with higher expression in diaphragm than sternohyoid are indicated in green. Numbers indicate fold-differential expression.

Figure 4

Extent of differential expression between sternohyoid and diaphragm muscle of carbohydrate metabolism genes. Left panel depicts data for 13 genes with higher expression in sternohyoid than diaphragm muscle; right panel depicts data for 11 genes with higher expression in diaphragm than sternohyoid muscle.

Figure 5

Genes with differential expression between sternohyoid and diaphragm muscle that are involved in specific steps of glycogen metabolism. Genes with higher expression in sternohyoid than diaphragm are indicated in red; genes with higher expression in diaphragm than sternohyoid are indicated in green. Numbers indicate fold-differential expression.