Feeding frequency affects glucose and lipid metabolism through SIRT1/AMPK pathway in growing pigs with the same amount of daily feed

Eating patterns are associated with obesity and metabolic health. However, the regulating mechanism of different eating patterns on body metabolism are not fully cleare. In this study, a pig model was used to evaluate the effects of feeding frequency on glucose and lipid metabolism and reveal its regulating mechanism. Twenty-four growing barrows were randomly allocated to 1-meal (M1), 3-meal (M3), or 5-meal (M5) per day groups with the same amount of daily feed. GSEA was conducted on the liver to investigate the pathways of different feeding frequencies on the metabolism. The serum glucose, NEFA, VLDL-C levels were higher for M1 group than for M3 and M5 groups, however, the hepatic TRIG level was lower. Liver transcriptome showed that glycolysis/gluconeogenesis and fatty acid metabolism pathways were suppressed with the increase of feeding frequency. The increase of gluconeogenic substrates (glycerol and lactate) and enzymes (PEPCK1 and G6Pase) in liver indicated that hepatic gluconeogenesis was enhanced in the M1 group. AMPK/PPARα signaling associated genes were positively correlated with NEFA and β-HB levels in M1 group, which promoted fatty acid oxidation and ketogenesis in liver. Moreover, compared with M3 and M5 groups, the higher NAD+/NADH ratio in the liver of M1 group activated SIRT1, which stimulated the AMPK signaling associated pathways by up-regulating the LKB1 gene. These findings provide evidence for the regulating roles of feeding frequency on glucose and lipid metabolism through SIRT1/AMPK pathway, which greatly contributes to the regulation of energy metabolism through daily eating patterns in animals.