title: Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases.
abstract: Fructose is associated with the biochemical alterations that promote the development of metabolic syndrome (MetS), nonalcoholic fatty liver disease, and type 2 diabetes. Its consumption has increased in parallel with MetS. It is metabolized by the liver, where it stimulates de novo lipogenesis. The triglycerides synthesized lead to hepatic insulin resistance and dyslipidemia. Fructose-derived advanced glycation end products (AGEs) may be involved via the Maillard reaction. Fructose has not been a main focus of glycation research because of the difficulty in measuring its adducts, and, more importantly, because although it is 10 times more reactive than glucose, its plasma concentration is only 1% of that of glucose. In this focused review, I summarize exogenous and endogenous fructose metabolism, fructose glycation, and in vitro, animal, and human data. Fructose is elevated in several tissues of diabetic patients where the polyol pathway is active, reaching the same order of magnitude as glucose. It is plausible that the high reactivity of fructose, directly or via its metabolites, may contribute to the formation of intracellular AGEs and to vascular complications. The evidence, however, is still unconvincing. Two areas that have been overlooked so far and should be actively explored include the following: 1) enteral formation of fructose AGEs, generating an inflammatory response to the receptor for AGEs (which may explain the strong association between fructose consumption and asthma, chronic bronchitis, and arthritis); and 2) inactivation of hepatic AMP-activated protein kinase by a fructose-mediated increase in methylglyoxal flux (perpetuating lipogenesis, fatty liver, and insulin resistance). If proven correct, these mechanisms would put the fructose-mediated Maillard reaction in the limelight again as a contributing factor in chronic inflammatory diseases and MetS.
authors.affiliation: Glycation, Oxidation, and Disease Laboratory, Department of Research, College of Osteopathic Medicine, Touro University California, Vallejo, CA alejandro.gugliucci@tu.edu.
authors.forename: Alejandro
authors.identifier: 0000-0001-5532-7535
authors.initials: A
authors.lastname: Gugliucci
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000139:chemically induced; D004195:Disease Models, Animal; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects; D024821:Metabolic Syndrome / Q000097:blood* / Q000139:chemically induced; D009765:Obesity / Q000097:blood* / Q000139:chemically induced; D013012:Sorbitol / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D014527:Uric Acid; D005632:Fructose; D013012:Sorbitol; D000255:Adenosine Triphosphate
keywords: AMPK; Maillard reaction; RAGE; advanced glycation; arthritis; asthma; diabetes; fructose; inflammation; metabolic syndrome