Abstract
Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic changes in the visceral adipose tissue of hereditary hypetriglyceridaemic rats, a non-obese model of metabolic syndrome. Compared to controls, 4-week intragastric MG administration impaired glucose tolerance (p < 0.05) and increased glycaemia (p < 0.01) and serum levels of MCP-1 and TNFα (p < 0.05), but had no effect on serum adiponectin or leptin. Adipose tissue insulin sensitivity and lipolysis were impaired (p < 0.05) in MG-treated rats. In addition, MG reduced the expression of transcription factor Nrf2 (p < 0.01), which controls antioxidant and lipogenic genes. Increased expression of Mcp-1 and TNFα (p < 0.05) together with activation of the SAPK/JNK signaling pathway can promote chronic inflammation in adipose tissue. Transcriptome network analysis revealed the over-representation of genes involved in insulin signaling (Irs1, Igf2, Ide), lipid metabolism (Nr1d1, Lpin1, Lrpap1) and angiogenesis (Dusp10, Tp53inp1).
Highlights
Metabolic changes and dysregulation in white adipose tissue (WAT) can trigger and considerably contribute to the development of metabolic diseases, such as metabolic syndrome, type 2 diabetes and associated complications
At the beginning of the study and before MG administration, we observed no differences in body weight, serum glucose or triglycerides between both groups of hereditary hypetriglyceridaemic (HHTg) rats
In HHTg rats, MG administration did not alter body weight. It did aggravate glucose intolerance, with non-fasting glucose and serum insulin significantly increased in MG-treated animals (Table 1)
Summary
Metabolic changes and dysregulation in white adipose tissue (WAT) can trigger and considerably contribute to the development of metabolic diseases, such as metabolic syndrome, type 2 diabetes and associated complications. As a result of various types of adipokine secretion, WAT regulates lipid and glucose metabolism, food intake and energy expenditure [1,2]. It is one of the first organs in which insulin resistance develops as a consequence of excessive and impaired lipid accumulation, leading to hypoxia and activation of inflammatory pathways. Apart from hypoxia, glycation is among the early pathological factors of adipose tissue dysfunction [3]. It has been shown that glycation processes can induce structural and morphological
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