Novel insights in intestinal and hepatic fructose metabolism: from mice to men

Evi Koene, Vera B Schrauwen-Hinderling, Patrick Schrauwen, Martijn C G J Brouwers*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

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Abstract

PURPOSE OF REVIEW: The rise in fructose consumption in parallel with the current epidemic of obesity and related cardiometabolic disease requires a better understanding of the pathophysiological pathways that are involved.

RECENT FINDINGS: Animal studies have shown that fructose has various effects on the intestines that subsequently affect intrahepatic lipid accumulation and inflammation. Fructose adversely affects the gut microbiome - as a producer of endotoxins and intermediates of de novo lipogenesis - and intestinal barrier function. Furthermore, intestinal fructose metabolism shields fructose away from the liver. Finally, fructose 1-phosphate (F1-P) serves as a signal molecule that promotes intestinal cell survival and, consequently, intestinal absorption capacity. Intervention and epidemiological studies have convincingly shown that fructose, particularly derived from sugar-sweetened beverages, stimulates de novo lipogenesis and intrahepatic lipid accumulation in humans. Of interest, individuals with aldolase B deficiency, who accumulate F1-P, are characterized by a greater intrahepatic lipid content. First phase II clinical trials have recently shown that reduction of F1-P, by inhibition of ketohexokinase, reduces intrahepatic lipid content.

SUMMARY: Experimental evidence supports current measures to reduce fructose intake, for example by the implementation of a tax on sugar-sweetened beverages, and pharmacological inhibition of fructose metabolism to reduce the global burden of cardiometabolic disease.

Original languageEnglish
Pages (from-to)354-359
Number of pages6
JournalCurrent Opinion in Clinical Nutrition and Metabolic Care
Volume25
Issue number5
Early online date16 Jul 2022
DOIs
Publication statusPublished - Sept 2022

Keywords

  • DIETARY FRUCTOSE
  • GLUCOKINASE
  • GLUCOSE
  • INHIBITION
  • KETOHEXOKINASE
  • LIPOGENESIS
  • LIVER FAT
  • MICROBIOTA
  • SUGAR
  • aldolase B
  • colorectal cancer
  • fructose
  • ketohexokinase
  • nonalcoholic fatty liver disease

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