Integration of metabolomics and transcriptomics to reveal metabolic characteristics and the role of mTORC1 in β-cell proliferation induced by a short-term high-fat diet.

Background: Pancreatic β-cell proliferation is essential for maintaining the balance of β-cell mass, and an elevated metabolic load can stimulate their proliferation. Numerous studies have shown that a short-term high-fat diet increases metabolic load without affecting insulin sensitivity, thereby promoting the proliferation of pancreatic β-cells. However, the underlying mechanisms of this effect remain to be fully elucidated. Results: A model has been constructed in our study to emulate pancreatic β-cell proliferation induced by a short-term high-fat diet, aiming to scrutinize the underlying mechanisms. Integrated transcriptomic and metabolomic analyses suggest that the mTORC1 signaling pathway may be crucial in this induced proliferation. Further analysis revealed that rapamycin, a specific inhibitor of the mTORC1 pathway, can inhibit proliferation induced by the short-term high-fat diet. Conclusion: Our study confirms the significant role of the mTORC1 signaling pathway in pancreatic β-cell proliferation induced by a short-term high-fat diet.