An integrative multiomics approach to characterize anti‐adipogenic and anti‐lipogenic effects of Akkermansia muciniphila in adipocytes

The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular‐based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3‐L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis. Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3‐L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics‐based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti‐lipogenic agents. Graphical and Lay Summary We investigated the changes of biological mechanisms in adipocytes after the treatment with the cell lysate of A. muciniphila, using multiomics analysis. The bacterial lysate decreased the expression levels in adipogenesis, lipogenesis and energy metabolism. In particular, the upregulation of SERPINA3G was positively correlated with the inhibition of lipid accumulation in adipocytes treated with the cell lysate of A. muciniphila.