CAMKK2-AMPK axis endows dietary calcium and phosphorus levels with regulatory effects on lipid metabolism in weaned piglets

Background In the realm of swine production, optimizing body composition and reducing excessive fat accumulation is critical for enhancing both economic efficiency and meat quality. Despite the acknowledged impact of dietary calcium (Ca) and phosphorus (P) on lipid metabolism, the precise mechanisms behind their synergistic effects on fat metabolism remain elusive. Results Research observations have shown a decreasing trend in the percentage of crude fat in carcasses with increased calcium and phosphorus content in feed. Concurrently, serum glucose concentrations significantly decreased, though differences in other lipid metabolism-related indicators were not significant across groups. Under conditions of low calcium and phosphorus, there is a significant suppression in the expression of FABPs, CD36 and PPARγ in the jejunum and ileum, leading to inhibited intestinal lipid absorption. Concurrently, this results in a marked increase in lipid accumulation in the liver. Conversely, higher levels of dietary calcium and phosphorus promoted intestinal lipid absorption and reduced liver lipid accumulation, with these changes being facilitated through the activation of the CAMKK2/AMPK signaling pathway by high-calcium-phosphorus diets. Additionally, the levels of calcium and phosphorus in the diet significantly altered the composition of liver lipids and the gut microbiota, increasing α-diversity and affecting the abundance of specific bacterial families related to lipid metabolism. Conclusion The evidence we provide indicates that the levels of calcium and phosphorus in the diet alter body fat content and lipid metabolism by modulating the response of the gut-liver axis to lipids. These effects are closely associated with the activation of the CAMKK2/AMPK signaling pathway.