Hepatic gluconeogenesis and regulatory mechanisms in lactating ruminants: A literature review

Abstract The conversion of various non‐sugar substances, such as propionate and lactate, produced by rumen microbial fermentation into glucose by hepatic gluconeogenesis is the main way to ensure an adequate supply of glucose to the mammary gland of ruminants. Unlike monogastric animals, in ruminants, hepatic gluconeogenesis is a continuous and efficient physiological process. Some signaling pathways, transcription factors, and nutrients affect the expression of genes encoding for gluconeogenic rate‐limiting enzymes, which in turn are involved in the regulation of hepatic gluconeogenesis. Although hepatic gluconeogenesis in ruminants has been researched for decades, it still needs to be clarified in depth. Therefore, this review summarizes the process, substrates, and regulatory mechanisms of hepatic gluconeogenesis in ruminants and establishes a theoretical basis for the development of precise nutritional regulation strategies to facilitate high‐quality high‐efficiency lactation. According to the research so far, phosphoenolpyruvate carboxy kinase, fructose‐1,6‐bisphosphatase, and glucose‐6‐phosphatase have been highlighted as the main rate‐limiting enzymes that determine the efficiency of gluconeogenesis. With regard to the underlying mechanisms, protein kinase A, protein kinase B, adenosine 5′‐monophosphate kinase, and mammalian target of rapamycin pathways have been found to regulate the expression of key gluconeogenic genes through transcription factors. Further, supplementation with propionate, certain amino acids, and micronutrients has shown beneficial effects in terms of improving efficiency of gluconeogenesis. Given the complexity of the metabolic pathways involved in hepatic gluconeogenesis in periparturient ruminants, further research is warranted on the regulatory mechanisms involved and the effects of supplementation with various nutrients on milk yield and animal health.