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Cited by 85Diet, Metabolism, and DiseaseMetabolism, Diabetes, and CancerLiver Disease Diagnosis and Treatment

Insights into the Hexose Liver Metabolism—Glucose versus Fructose

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Geidl-Flueck, Bettina, Gerber, Philipp·2017·Nutrients
DOI 10.3390/nu9091026PMC PMC5622786
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Abstract

High-fructose intake in healthy men is associated with characteristics of metabolic syndrome. Extensive knowledge exists about the differences between hepatic fructose and glucose metabolism and fructose-specific mechanisms favoring the development of metabolic disturbances. Nevertheless, the causal relationship between fructose consumption and metabolic alterations is still debated. Multiple effects of fructose on hepatic metabolism are attributed to the fact that the liver represents the major sink of fructose. Fructose, as a lipogenic substrate and potent inducer of lipogenic enzyme expression, enhances fatty acid synthesis. Consequently, increased hepatic diacylglycerols (DAG) are thought to directly interfere with insulin signaling. However, independently of this effect, fructose may also counteract insulin-mediated effects on liver metabolism by a range of mechanisms. It may drive gluconeogenesis not only as a gluconeogenic substrate, but also as a potent inducer of carbohydrate responsive element binding protein (ChREBP), which induces the expression of lipogenic enzymes as well as gluconeogenic enzymes. It remains a challenge to determine the relative contributions of the impact of fructose on hepatic transcriptome, proteome and allosterome changes and consequently on the regulation of plasma glucose metabolism/homeostasis. Mathematical models exist modeling hepatic glucose metabolism. Future models should not only consider the hepatic adjustments of enzyme abundances and activities in response to changing plasma glucose and insulin/glucagon concentrations, but also to varying fructose concentrations for defining the role of fructose in the hepatic control of plasma glucose homeostasis.

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  • Free sugars stimulate hepatic triglyceride synthesis (fructose more so than glucose) via a stimulatory effect on de novo lipogenesis and VLDL secretion.

    “Free sugars stimulate hepatic triglyceride synthesis (fructose more so than glucose) via a stimulatory effect on de novo lipogenesis and VLDL secretion.”

    From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [81]

    Section 6 (TAG Synthesis and VLDL Secretion; page not provided) describes fructose-induced fatty acid synthesis as a proposed route to greater hepatic TAG synthesis and VLDL secretion. Section 4 (Lipogenesis; page not provided) suggests fructose may provide more lipogenic substrate than glucose. The claim presents these effects as established for free sugars generally, whereas the Conclusions say effects depend on dose and energy intake and that findings on VLDL secretion under energy-balanced high-fructose diets are inconsistent. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Fructose may impair postprandial triglyceride clearance due to decreased insulin levels (via decreased secretion) and decreased lipoprotein lipase activity.

    “Fructose may also impair postprandial triglyceride clearance due to decreased insulin levels (via decreased secretion) and decreased lipoprotein lipase activity (81).”

    From 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia (2021) · cites this paper as [81]

    Section 6, “TAG Synthesis and VLDL Secretion” (page unavailable), says high-fructose intake may impair postprandial TAG clearance through decreased insulin levels and consequently decreased lipoprotein lipase activity. It does not say that the lower insulin levels result from decreased secretion; the passages on insulin secretion do not establish that link. (LLM, conf=0.87)

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Authors
Geidl-Flueck, B., & Gerber, P.
Affiliations
  • Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, 8091 Zurich, Switzerland
  • University Hospital Zurich (CH)
ORCID
Gerber, Philipp
Venue
Nutrients
Publisher
MDPI AG
Published
2017-09-16
Volume
9
Issue
9
Pages
1026
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu9091026
PMC
PMC5622786
OpenAlex
W2755184413
Cited by
85
References
147
Citations by year
2026: 4 · 2025: 9 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 17 · 2018: 9 · 2017: 1
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Swiss National Science Foundation (144204)
  • Vontobel-Stiftung
  • Promedica Stiftung
  • Uniscientia Stiftung
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
fructose metabolism, hepatic glucose metabolism, metabolic syndrome, hepatic lipogenesis, fatty acid synthesis, diacylglycerol, insulin signaling, gluconeogenesis, ChREBP, liver transcriptome, high fructose intake
MeSH terms
X-Box Binding Protein 1, Animals, Disease Models, Animal, Fructose, Glucagon, Gluconeogenesis, Glucose, Humans, Insulin, Liver, Triglycerides, Meta-Analysis as Topic, Lipogenesis, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Sterol Regulatory Element Binding Protein 1

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