Abstract
Rising levels of obesity in the United States (US) and in nations adopting a Western diet are of concern due to the associated risk of chronic diseases. As an endocrine organ, adipose tissue regulates whole body immunity and energy homeostasis, but during obesity, disruptions in the normal metabolism of adipocytes, such as increased oxidative stress and reduced mitochondrial function, may contribute to disease development. Diets high in added sugar, particularly sucrose and high fructose corn syrup, may induce metabolic abnormalities in adipocytes by increasing the rate of glycolysis and the accumulation of glycolytic metabolites. Methylglyoxal (MG), a highly reactive metabolite of glycolysis, damages proteins and other cellular components. MG is found at higher concentrations in the serum and tissues of individuals with diabetes and is directly involved in the pathophysiology of diabetic complications, however, MG may have negative effects on cell metabolism before the onset of disease. Recent studies using animal models suggest MG accumulates in adipose tissue during high fructose feeding and impairs insulin signaling pathways. However, the specific effects of MG in adipocytes require further investigation. The objective of this study was to characterize changes in the proteome of mature adipocytes exposed to non‐toxic levels of MG. We treated fully differentiated 3T3‐L1 adipocytes with either MG or PBS as a control for 48 hours. Cells were collected, delipidated, and proteins precipitated. After denaturation, in‐solution protein digestion was performed with trypsin and the resulting peptide fragments were separated by liquid chromatography and scanned by mass spectrometry (MS), followed by additional MS/MS scanning. MS/MS data was analyzed with MaxQuant software and proteins identified by comparison with the Uniprot mouse database. The proteome of MG‐treated adipocytes was characterized by reduced expression of both mitochondria‐related proteins and proteins involved in endogenous antioxidant pathways. In addition, MG treatment altered the expression of proteins involved in several key metabolic pathways, including oxidative phosphorylation, the citric acid cycle, and pyruvate metabolism. We conclude that MG induces changes in adipocytes which may not only contribute to oxidative stress, but which may disrupt normal metabolic pathways. Though this may represent a temporary adaptation to MG exposure, over time, repeated such exposures may make adipocytes more vulnerable to the serious metabolic abnormalities known to be associated with obesity‐related diseases.Support or Funding InformationUSDA NIFA grant #2011‐38420‐20038, Core Pilot grant Indiana Clinical and Translational Sciences Institute #UL1TR001108
Published Version
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