Carbohydrate Deprivation Improves Glycolipid Metabolism and Activates AMPK/PGC1α Signaling Pathway in Mice

Carbohydrate intake profoundly shapes hepatic metabolism, impacting crucial pathways like glycolysis, lipogenesis, and ketogenesis. This study aimed to investigate the effects of carbohydrate deprivation on hepatic glycolipid metabolism in mice.

Male C57BL/6J mice were subjected to a 4-week dietary intervention where they were assigned to one of four groups: standard diet (CON), low-carbohydrate high-fat diet (LCD), no-carbohydrate high-fat diet (NCD), and high-carbohydrate no-fat diet (HCD). Post-intervention analysis revealed that the NCD group exhibited reduced blood glucose, HbA1c, and LDL-C levels compared to the CON group. Additionally, the NCD group showed decreased liver glycogen content and liver index. Histopathological examination of liver sections indicated less lipid accumulation and a significant down-regulation of hepatic de novo lipogenesis (DNL)-related proteins in the NCD group. Metabolomics analysis demonstrated higher hepatic acylcarnitine levels and lower lysophosphatidylcholine and fatty acyl metabolites levels in the NCD group. Furthermore, protein expression levels of pAMPK, pHSL, PGC1α, CPT1A, and OXPHOS were elevated in the NCD group, suggesting enhanced hepatic energy metabolism and lipolysis ability.

These findings suggested that carbohydrate deprivation enhances fatty acid metabolism capacity and inhibits lipogenesis via the AMPK/PGC1α pathway to improve glucose and lipid metabolism in mice.