Leptin (LEP), a protein hormone well-known for its role in metabolic regulation, has recently been linked to lipid metabolism in cattle. However, its function in buffalo mammary glands remains unclear. To address this issue, we isolated and identified the LEP gene and conducted experiments to investigate its function in buffalo mammary epithelial cells (BuMECs). In this study, two transcript variants of LEP, designated as LEP_X1 and LEP_X2, were identified. The coding sequences (CDS) of LEP_X1 and LEP_X2 are 504 bp and 579 bp in length, encoding 167 and 192 amino acid residues, respectively. Bioinformatics analysis revealed that LEP_X2 is a hydrophobic protein with an isoelectric point below 7 and contains a signal peptide, while LEP_X1 is hydrophilic and lacks a signal peptide. Our study found that LEP gene expression in lactating BuMECs was significantly higher than in non-lactating cells, with LEP_X2 expression remarkably higher than LEP_X1 in lactating BuMECs. Overexpression of both LEP_X1 and LEP_X2 significantly promoted the expression of genes related to milk fat synthesis in lactating BuMECs, including STAT3, PI3K, mTOR, SCD, and SREBF1, accompanied by an increase in cellular triglycerides (TG). Interestingly, LEP_X2 overexpression significantly suppressed LEP_X1 expression while increasing intracellular TG concentration by 12.10-fold compared to LEP_X1 overexpression, suggesting an antagonistic relationship between the two variants and supposing LEP_X2 plays a dominant role in milk fat synthesis in lactating BuMECs. Additionally, four nucleotide substitutions were identified in the buffalo LEP CDS, including a nonsynonymous substitution c.148C>T (p.Arg50Cys), which was predicted to decrease the stability of the LEP protein without affecting its function. These results collectively underscore the significant role of LEP in milk fat synthesis and can provide a basis for molecular breeding strategies of buffalo.

Domestic cattle represent one of the most significant evolutionary successes in the history of human–animal mutualism. This review synthesizes evidence from paleogenomics and modern population genetics, particularly recent pangenome analyses, to reconstruct a comprehensive evolutionary trajectory of cattle. We outline the two domestication events: the emergence of taurine cattle (Bos taurus) in the Fertile Crescent (~10,500 years ago) and zebu cattle (Bos indicus) in the Indus Valley (~8000 years ago). Following domestication, cattle dispersed globally alongside human migration, resulting in a complex genetic mosaic shaped by introgression with wild relatives and extensive admixture between lineages. By integrating data from mitochondrial DNA, Y-chromosome haplotypes, and whole-genome sequencing of modern, ancient, and wild samples, we reconstruct the detailed global dispersal of cattle. Furthermore, we dissect the molecular mechanisms underlying phenotypic diversity, emphasizing how natural selection has driven environmental adaptation, how artificial selection has optimized production traits, and how the emerging bovine pangenome is unveiling “hidden” genetic variations critical for climate resilience and disease resistance. Ultimately, this review summarizes the origin, dispersal, and genomic diversity of cattle, offering vital insights for the conservation of indigenous genetic resources and the advancement of molecular breeding strategies in the face of a changing global climate.