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Developmental biology - Diabetes

Fructose doesn't affect our body like sugar does

In mice, fructose, sugar from fruit, is processed mainly in the small intestine, not in the liver as once thought...


Sugary drinks and processed high-sugar foods (such as iced donuts, cakes, and candy) overwhelm the small intestine and spill into our liver for more processing. But, scientists have learned that the ability of our small intestine to process fructose is higher after a meal. Their work appears February 6 in the journal Cell Metabolism.

Evidence from previous animal and human studies has shown that eating excessive amounts of sugar can be harmful, especially to our liver. Chronic over-consumption can lead to obesity and foster insulin resistance which can progress to diabetes. It can also contribute to non-alcoholic fatty liver disease, which can lead to cirrhosis or even liver cancer.

"There is a fundamental physiological difference in how smaller and larger amounts of sugar are processed in the body," explains Joshua D. Rabinowitz of the Lewis-Sigler Institute for Integrative Genomics at Princeton University, whose laboratory led the study. Previous to this study, the view was that our liver processes all ingested sugar.
However, this study shows that more than 90 percent of fructose is cleared by the small intestine in mice.

"We can offer some reassurance, at least from these animal studies, that fructose from moderate amounts of fruits will not reach the liver," explains Rabinowitz.

However, the small intestine probably starts to get overwhelmed with sugar halfway through a can of soda or one large glass of orange juice.

In the study, the path of isotope-labeled fructose was followed through the digestive systems of laboratory mice. Researchers saw that excess fructose not absorbed by the small intestine continues into the colon. As a consequence, it also comes into contact with the natural microbiotic flora of the large intestine and colon, known as the microbiome.
"The microbiome is designed to never see sugar. One can eat an infinite amount of carbohydrates, and there will be nary a molecule of glucose that enters the microbiome. But as soon as you drink the soda or juice, the microbiome is seeing an extremely powerful nutrient that it was designed to never see."

Joshua D. Rabinowitz PhD, Lewis-Sigler Institute for Integrative Genomics,Department of Chemistry, Princeton University, Princeton, New Jersey, USA.

While the study did not show that fructose influences the microbiome, its authors suggest an effect is likely and should be studied further to learn more about the biological consequences of high sugar intake. Investigators also found that the mouse small intestine clears fructose more efficiently after eating a meal.
"We saw that feeding the mice prior to their sugar exposure enhanced their small intestine's ability to process fructose and protected their liver and microbiome from sugar exposure."

Joshua D. Rabinowitz PhD.

Researchers theorize that in a fasting state, such as just after waking or in mid-afternoon, our body too, is extra vulnerable to fructose due to its lessened ability to process fructose in our small intestine.

Although the study was conducted in mice, Rabinowitz encourages "the most old-fashioned advice in the world" for humans. Limit sweets to moderate quantities after meals, and do not have sweet drinks away from meal time.

Highlights
Isotope tracing reveals that the small intestine metabolizes most dietary fructose
High-dose fructose saturates intestinal fructose clearance capacity
Excess fructose spills over to the liver and colonic microbiota
Intestinal fructose clearance is enhanced by feeding

Summary
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ~90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood. High doses of fructose (>=1 g/kg) overwhelm intestinal fructose absorption and clearance, resulting in fructose reaching both the liver and colonic microbiota. Intestinal fructose clearance is augmented both by prior exposure to fructose and by feeding. We propose that the small intestine shields the liver from otherwise toxic fructose exposure.

Authors: Cholsoon Jang, Sheng Hui, Wenyun Lu, Alexis J. Cowan, Raphael J. Morscher, Gina Lee, Wei Liu, Gregory J. Tesz, Morris J. Birnbaum, Joshua D. Rabinowitz.


Acknowledgements
The research was supported by the American Diabetes Association, the Life Sciences Research Foundation, and the LAM Foundation. Several co-authors are employees of Pfizer, Inc.

Cell Metabolism (@Cell_Metabolism), published by Cell Press, is a monthly journal that publishes reports of novel results in metabolic biology, from molecular and cellular biology to translational studies. The journal aims to highlight work addressing the molecular mechanisms underlying physiology and homeostasis in health and disease. Visit: http://www.cell.com/cell-metabolism. To receive Cell Press media alerts, contact press@cell.com.


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Jun 11, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




This graphic depicts how the small intestine actually clears most dietary fructose. Higher fructose amounts spill over to the liver and into colonic microbiota to be further metabolized.
Image credit: Jang et al./Cell Metabolism 2018


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