Metformin alters liver metabolism to sustain egg production in the reproductively aging broiler breeder hen
The liver plays a critical role in avian reproduction as it is the primary site of de novo lipogenesis and yolk precursor synthesis. Broiler breeder hens, the parents of commercial broiler chickens, often experience poor reproductive efficiency primarily due to declining egg production beginning around 45 weeks of age. Metformin, an antidiabetic drug, exerts its primary effects in the liver by increasing insulin sensitivity and reducing hepatic glucose production in humans. This study aimed to characterize the liver transcriptomic profile of broiler breeder hens supplemented with metformin in the diet at 0 or 75 mg/kg body weight for 40 weeks (25-65 weeks of age; n=45 hens/treatment). Liver tissue was collected from a subset of hens (n=12 hens/treatment group) at 65 weeks of age, RNA was extracted and sequenced using next-generation sequencing. Differential gene abundance analysis revealed that metformin treatment led to the most significant changes in gene expression, with 552 genes differentially expressed compared to the control group. Further transcriptomic analysis highlighted increased expression of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis. qPCR analysis revealed increased expression of ESR1, APOB, APOV1, VTG2, ADIPOQ, ADIPOR2 and ACACA mRNA and decreased expression of PCK1 mRNA validating the transcriptomic data. Collectively, the present study suggests that metformin supplementation supports prolonged egg production in aging broiler breeder hens by sustaining yolk precursor and fatty acid synthesis that are typically diminished in aging broiler breeder hens. Overall design: RNA-seq profiling of liver tissue collected from broiler breeder hens supplemented with metformin (0 or 75 mg/kg body weight) in the diet for 40 weeks (25-65 weeks of age).