Novel Contributions to Understanding Hepatic Gluconeogenic Enzyme Regulation During Severe Negative Energy Balance in Periparturient Dairy Cattle in Kaduna State, North West Nigeria

The regulation of hepatic gluconeogenesis is central to survival in periparturient dairy cattle experiencing severe negative energy balance, yet the molecular dynamics of key gluconeogenic enzymes including phosphoenolpyruvate carboxykinase and pyruvate carboxylase during this critical transition period have not been characterised in Nigerian cattle populations. This study investigated hepatic gluconeogenic enzyme activity, gene expression, and their upstream hormonal regulators in Friesian-Zebu crossbred cows classified as severely negative energy balanced during the periparturient period at a commercial dairy enterprise in Kaduna State. Sixty cows were enrolled, with hepatic biopsies obtained by ultrasound-guided percutaneous needle technique at three weeks prepartum, at calving, and at weeks one and three postpartum. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase activities were quantified by kinetic enzyme assay, and messenger RNA expression was measured by quantitative reverse-transcription PCR. Upstream regulators including insulin, glucagon, cortisol, and peroxisome proliferator-activated receptor-alpha were quantified by enzyme-linked immunosorbent assay. Phosphoenolpyruvate carboxykinase activity increased fourfold from prepartum to week one postpartum, while messenger RNA expression showed a fivefold induction, implicating transcriptional regulation. Cortisol and glucagon were the primary positive regulators in regression models, while insulin retained a suppressive role despite marked hypoinsulinaemia. Peroxisome proliferator-activated receptor-alpha activation correlated with peak enzyme expression. These original findings advance mechanistic understanding of gluconeogenic regulation in transition cattle and provide novel therapeutic targets for addressing negative energy balance in North West Nigeria. Keywords: gluconeogenesis, phosphoenolpyruvate carboxykinase, negative energy balance, periparturient cattle, Kaduna.