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Cited by 225Advanced Glycation End Products researchDiet, Metabolism, and DiseasePotato Plant Research

The DOI matches its Crossref record; 101 of the 105 references it cites were found in a registry or an index.

Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases

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Gugliucci, Alejandro·2017·Advances in Nutrition
DOI 10.3945/an.116.013912PMC PMC5227984
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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.

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Crossref · 10.3945/an.116.013912

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Figures

FIGURE 1 Fructose metabolism in hepatocytes. Numbers indicate key reactions and are explained in text. Glut, glucose transporter; P, phosphate.
FIGURE 1 Fructose metabolism in hepatocytes. Numbers indicate key reactions and are explained in text. Glut, glucose transporter; P, phosphate.CC-BY-NC-ND · From the PDF
FIGURE 2 The sorbitol pathway as an intracellular source, and dietary sources of fructose and AGEs. Question marks indicate areas in which our knowledge or evidence is scant. Dietary fructose is mainly kept at the liver at first pass; therefore, the role of circulating fructose in AGE formation is questionable. AGE, advanced glycation end product; Fru-AGE, fructose-advanced glycation end product; GI, gastrointestinal; G-6-P, glucose-6phosphate.
FIGURE 2 The sorbitol pathway as an intracellular source, and dietary sources of fructose and AGEs. Question marks indicate areas in which our knowledge or evidence is scant. Dietary fructose is mainly kept at the liver at first pass; therefore, the role of circulating fructose in AGE formation is questionable. AGE, advanced glycation end product; Fru-AGE, fructose-advanced glycation end product; GI, gastrointestinal; G-6-P, glucose-6phosphate.CC-BY-NC-ND · From the PDF
Image 3
CC-BY-NC-ND · From the PDF
FIGURE 4 Two areas of fructose-mediated Maillard reaction that have been overlooked. Enteral formation of fructose AGEs, generating an RAGE inflammatory response (A); inactivation of hepatic AMPK by a fructose-mediated increase in methylglyoxal flux (B). AcCoA, acetyl coenzyme A; AGE, advanced glycation end product; AMPK, AMP-activated protein kinase; MG, methylglyoxal; RAGE, receptor for advanced glycation end products.
FIGURE 4 Two areas of fructose-mediated Maillard reaction that have been overlooked. Enteral formation of fructose AGEs, generating an RAGE inflammatory response (A); inactivation of hepatic AMPK by a fructose-mediated increase in methylglyoxal flux (B). AcCoA, acetyl coenzyme A; AGE, advanced glycation end product; AMPK, AMP-activated protein kinase; MG, methylglyoxal; RAGE, receptor for advanced glycation end products.CC-BY-NC-ND · From the PDF

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Metadata

Authors
Gugliucci, A.
Affiliations
Touro University California (US)
Corresponding author
Gugliucci, Alejandro
ORCID
Gugliucci, Alejandro
Venue
Advances in Nutrition
Publisher
Elsevier BV
Published
2017-01
Volume
8
Issue
1
Pages
54-62
ISSN
  • 2156-5376 (ISSN-L)
  • 2161-8313
DOI
10.3945/an.116.013912
PMC
PMC5227984
OpenAlex
W2572954835
Cited by
225
References
105
Citations by year
2026: 7 · 2025: 24 · 2024: 31 · 2023: 24 · 2022: 32 · 2021: 36 · 2020: 20 · 2019: 26 · 2018: 14 · 2017: 8
FWCI
2.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Advances in Nutrition (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Touro Scholar (Touro College) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
Keywords
fructose, advanced glycation end products, Maillard reaction, metabolic syndrome, non-alcoholic fatty liver disease, type 2 diabetes, hepatic insulin resistance, de novo lipogenesis, polyol pathway, methylglyoxal, AMPK, receptor for advanced glycation end products, inflammation, asthma, chronic bronchitis, arthritis, vascular complications
MeSH terms
Adenosine Triphosphate, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Fructose, Humans, Obesity, Sorbitol, Uric Acid, Glycation End Products, Advanced, Metabolic Syndrome, Lipogenesis

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