Bighead carp (Hypophthalmichthys nobilis) is a key aquaculture species, with the head and its orbital fat being a commercially valuable product. To elucidate the molecular basis of growth variation, we performed comparative transcriptome analysis of orbital fat from extreme growth phenotypes at juvenile (6 months) and market-size (18 months) stages. In juveniles, slow growth was linked to upregulation of stress-responsive genes (sgk1, fkbp5, lipg), while fast growth correlated with higher expression of stress-buffering (crhbp) and nutrient-signaling (rbp2, mgea5) genes. At 18 months, divergent growth aligned with opposing lipid metabolic states: a pro-anabolic profile (dgat2, fads2) supported fast growth, whereas a catabolic profile (cpt1b, ppargc1a) was associated with slow growth. These results demonstrate stage-specific transcriptional reprogramming in orbital fat underlying growth variation. This study provides a molecular framework for orbital fat-mediated growth regulation and highlights potential candidate genes for molecular breeding in bighead carp.

The orbital fat of bighead carp (Hypophthalmichthys nobilis) represents a structural fat deposit located posterior to the eyes and constitutes an important edible component of the head region. Nevertheless, molecular mechanisms governing lipid accumulation during ontogenetic development remain insufficiently characterized. Here, we performed RNA-Seq on orbital fat tissues from 6-month-old (juvenile) and 18-month-old (market-size) bighead carp. A total of 1042 DEGs were identified, with 807 up-regulated and 235 down-regulated in the 6-month-old stage. Functional enrichment revealed key pathways including fatty acid metabolism, PPAR signaling, and glycolysis/gluconeogenesis. qRT-PCR validation confirmed RNA-Seq reliability. Notably, the differential expression patterns of genes such as cpt1a, cpt1b, slc27a1, fads2, and scd suggest their association with an elevated capacity for lipid synthesis in the orbital fat of 18-month-old bighead carp. This study presents the first transcriptome analysis of orbital fat development in a freshwater fish, offering insights into the genetic improvement of head meat quality traits and growth in bighead carp head.