Tissue-Specific Diversity of Nuclear-Encoded Mitochondrial Genes Related to Lipid and Carbohydrate Metabolism in Buffalo.

Buffaloes play a crucial role in Asian agriculture, enhancing food security and rural development. Their distinct metabolic needs drive tissue-specific mitochondrial adaptations, regulated by both mitochondrial and nuclear genomes. This study explores how nuclear-encoded mitochondrial genes involved in lipid and carbohydrate metabolism vary across tissues-an area with significant implications for buffalo health, productivity, and human health. We hypothesize that tissue-specific variations in metabolic pathways are reflected in the expression of nuclear-encoded mitochondrial genes, which are tailored to the metabolic needs of each tissue. We utilized high-throughput RNA sequencing (RNA-seq) data to assess the expression of nuclear-encoded mitochondrial genes related to lipid and carbohydrate metabolism across various tissues in healthy female buffaloes aged 3-5 years, including the kidney, heart, brain, and ovary. Differential expression analysis was performed using DESeq2, with significance set at p < 0.05 for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 164 genes exhibited tissue-specific regulation, with the heart and brain, which have higher energy demands, expressing more genes than the kidney and ovary. Notably, the comparison between the kidney and ovary showed the highest number of differentially expressed genes. Interestingly, the kidney up-regulates gluconeogenesis-related genes (e.g., PCK2, PCCA, LDHD), promoting glucose production, while these genes are down-regulated in the ovary. In contrast, the brain up-regulates pyruvate metabolism genes (e.g., PCCA, PDHA1, LDHD), underscoring its reliance on glucose as a primary energy source, while these genes are down-regulated in the ovary. The higher abundance of EHHADH in the brain compared to the ovary further emphasizes the critical role of fatty acid metabolism in brain function, aligned with the brain's high energy demands. Additionally, down-regulation of the StAR gene in both the kidney versus ovary and brain versus ovary comparisons suggests tissue-specific differences in steroid hormone regulation. These findings highlight tissue-specific variations in nuclear-encoded mitochondrial genes related to lipid and carbohydrate metabolism, reflecting adaptations to each tissue's unique metabolic needs. This study lays a foundation for advancing mitochondrial metabolism research in livestock, with significant implications for human health. Insights could inform dietary or therapeutic strategies for metabolic disorders, such as cardiovascular diseases and metabolic syndrome, while also enhancing livestock productivity.