Glycolaldehyde disrupts insulin signaling and glucose uptake through adipogenesis

Abstract

AbstractThe accumulation of advanced glycation end products (AGEs) plays critical roles in exacerbating obesity, arteriosclerosis, cardiovascular disease, diabetes, and their associated complications. Glycolaldehyde (GA) is the metabolic precursor of several AGEs, and its effects vary based on food and cooking methods. Here, 3T3-L1 adipocytes were used to examine the effects of GA on obesity and insulin resistance. We found that GA treatment did not increase lipid accumulation but increased the distribution of adipocyte differentiation. We also investigated the production of receptor for AGEs (RAGE) and reactive oxygen species (ROS) upon GA treatment, as well as the expression levels of peroxisome proliferator-activated receptors γ (PPARγ), CCAAT enhancer binding protein α (c/EBPα), and CCAAT enhancer binding protein β (c/EBPβ), which are transcription factors for adipogenesis, were significantly increased upon GA treatment in a concentration-dependent manner. GA arrested the cell cycle at the G0/G1 stage during the early phase of adipogenesis and suppressed the expression of p21 and p27. GA increased the expression of CDK2, phosphorylation of mitogen-activated protein kinases, and secretion of pro-inflammatory cytokines. Overall, these results suggest that GA can stimulate lipid metabolism, hence, we suggest that the stimulation of adipogenesis and insulin resistance by GA may be associated with the interaction between RAGE and adipogenic factors in adipocytes.