Abstract

The 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.

Highlights

  • Maillard reaction is a non-enzymatic reaction between reducing sugars and amino structures in amino acids, proteins, phospholipids, or DNA and is associated with age and severity of diabetes

  • Our findings show that GA induces obesity and insulin resistance through the Advanced glycation end products (AGE)–receptor for AGEs (RAGE) axis and reactive oxygen species (ROS) signaling in the adipogenesis process

  • Maillard reaction is a type of non-enzymatic browning that reduces carbonyl and carbonyl compounds, especially sugars, using free amino groups, such as amino acids, amines, and proteins [21]

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Summary

Introduction

Maillard reaction is a non-enzymatic reaction between reducing sugars and amino structures in amino acids, proteins, phospholipids, or DNA and is associated with age and severity of diabetes. GA concentrations in adipose tissue from healthy people or patients have not been quantified so far. The GA level of adipose tissue has not been quantified, its physiological concentration is estimated to range from. 0.2 to 2 mM and several in vitro studies have employed this range. Many previous studies have been conducted in various cell models at concentrations ranging from 0.2 to 2 mM. We have checked the reasonable reasons for the various concentrations used in many previous studies. We performed the screening in the adipocyte cell model using concentrations ranging from 0.2 to 2 mM. The production and accumulation of AGEs require large amounts of GA with steady accumulation in the adipose tissue. We applied an acute model to study adipogenesis caused by GA-derived AGEs at the cellular level

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