Deiodinase gene expression profiles underlie breed-specific thyroid metabolism and heat stress resilience in cattle

Heat stress represents a major constraint to cattle productivity in tropical environments. This study investigated expression of selected candidate genes related to thyroid metabolism, mitochondrial function, lipid metabolism, growth signalling, and stress response across three cattle genotypes to characterize breed-specific transcriptional profiles under natural peak heat-load conditions and explore their potential relevance to thyroid hormone metabolism and thermal adaptation. Whole blood RNA-seq was performed on samples collected from the three cattle breeds during peak heat load (Temperature-Humidity Index: 84.30; Heat Stress Index: 44.68 °C), conditions categorized as severe heat stress. Of 20 genes analyzed, 17 showed detectable differential regulation across the breeds. DIO2 and ADRB3 were significantly down regulated in HF compared with KK and BR (P < 0.01), whereas ELOVL3 was upregulated in HF (Log2FC = 6.96, P < 0.001), indicating distinct transcriptional profiles along the thyroid-adrenergic-lipid axis. Co-expression network analysis identified three tightly co-regulated modules (r > 0.9) including the lipid metabolism-thermogenesis, mitochondrial-oxidative metabolism, and growth-stress response. Lipid-thermogenic genes (CIDEA, SCD, ELOVL3) exhibited strong positive correlations (r > 0.8), while inverse relationships observed between thermogenic genes and growth regulators (GHR, PMAIP1) suggested metabolic trade-offs under heat stress. Functional enrichment analysis of these genes revealed mitochondrial function and lipid metabolism as predominant biological categories, with oxidative phosphorylation and fatty acid metabolism representing the most enriched pathways, linked through the thyroid-mitochondrial gene expression axis driving thermogenic adaptation in the breeds. These findings demonstrate that breed-specific heat resilience is associated with coordinated regulation of deiodinase pathways and integrated lipid-mitochondrial-stress networks. The identified genes, including DIO2, ADRB3, and ELOVL3, along with their co-expression modules, represent promising molecular targets for selecting cattle adapted to warming climates.

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