Proteomic profiling of metformin effects in 3T3-L1 adipocytes by SILAC-based quantification.

ABSTRACT

Metformin is a common and generally the first medication prescribed for treatment of type 2 diabetes. Its mechanism involves affecting pathways that regulate glucose and lipid metabolism in metabolic cells such as that of muscle and liver cells. In spite of various studies exploring its effects, the proteome changes in adipocytes in response to metformin remains poorly understood. In this study, we performed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic profiling to study the effects of metformin specifically on 3T3-L1 adipocytes. We define proteins that exhibited altered levels with metformin treatment, 400 of them showing statistically significant changes in our study. Our results suggest that metformin affects not only the PPAR signaling pathway, as well as glucose and lipid metabolism, but also protein folding, endoplasmic reticulum stress, negative regulation of appetite, and one-carbon folate metabolism in adipocytes. This proteomic investigation provides important insight into effects of metformin in adipocytes.