The gut shields the liver from fructose-induced damage

Date:
June 29, 2020
Source:
University of Pennsylvania School of Medicine
Summary:
After one consumes food or a beverage containing fructose, the
gastrointestinal system, or gut, helps to shield the liver from
damage by breaking down the sugar before it reaches the liver,
according to a new multi-center study. However, the consumption
of too much fructose - - particularly in a short period of time
-- can overwhelm the gut, causing fructose to ''spill over''
into the liver, where it wreaks havoc and causes fatty liver,
researchers discovered.



FULL STORY ========================================================================== After one consumes food or a beverage containing fructose, the
gastrointestinal system, or gut, helps to shield the liver from damage
by breaking down the sugar before it reaches the liver, according to
a new multi-center study led by researchers in the Perelman School of
Medicine at the University of Pennsylvania. However, the consumption
of too much fructose -- particularly in a short period of time -- can
overwhelm the gut, causing fructose to "spill over" into the liver,
where it wreaks havoc and causes fatty liver, researchers discovered.


==========================================================================
The findings, in mice, help to unravel longstanding questions about how
the body metabolizes fructose -- a form of sugar often found in fruits, vegetables, and honey, as well as most processed foods in the form of high fructose corn syrup. Consumption of fructose has increased 100-fold over
the last century, even as studies have shown that excessive consumption, particularly sweet drinks, are linked to non-alcoholic fatty liver
disease, obesity and diabetes.

The findings were published in Nature Metabolism.

"What we discovered and show here is that, after you eat or drink
fructose, the gut actually consumes the fructose first -- helping
to protect the liver from fructose-induced damage," said the study's corresponding author Zoltan Arany, MD, PhD, a professor of Cardiovascular Medicine at Penn. "Importantly, we also show that consuming the
food or beverage slowly over a long meal, rather than in one gulp,
can mitigate the adverse consequences." Studies have shown that the
excessive consumption of fructose can be toxic to the liver. When large quantities of fructose reach the liver, the liver uses excess fructose
to create fat, a process called lipogenesis. Eventually, people who
consume too much fructose can develop nonalcoholic fatty liver disease,
a condition in which too much fat is stored in the liver cells.

Until now, it hasn't been clear whether the gut's role in processing the fructose prevents or contributes to fructose-induced lipogenesis and the development of liver diseases. For this study, the team of researchers, including Princeton University's Joshua Rabinowitz, MD, PhD, studied
a key enzyme, called ketohexokinase, that controls how fast fructose
is consumed.

They showed, by genetically engineering mice, that lowering the levels
of this enzyme in the gut led to fatty livers in the mice. Conversely,
the team showed that increasing the level of ketohexokinase in the gut protected from fatty liver. Thus, the researchers found the breakdown of fructose in the gut mitigates the development of extra fat in liver cells
in mice. They discovered that the rate at which the intestine can clear fructose determines the rate at which fructose can be safely ingested.

In addition, the team showed the same amount of fructose is more likely
to result in the development of fatty liver when its consumed via a
beverage versus food. Similarly, one faces an increased likelihood
of developing fatty liver when consuming fructose in a single setting
compared to several doses spread over 45 minutes.

"Collectively, our findings show fructose induces lipogenesis when the
intake rate exceeds the gut's capacity to process fructose and protect
the liver," Arany said. "In the modern context of excessive availability
and consumption of processed foods, it is easy to see how the resulting fructose spillover would drive metabolic syndrome." Researchers noted
that more work is needed to determine the extent to which these findings
in mice extend to humans. Additional Penn authors include Shogo Wada,
Steven Yang and Bridget Gosis.

The research was supported, in part, by a grant from the DRC Regional Metabolomics Core (P30 DK19525), National Institutes of Health
(1DP1DK113643 and DK107667).


========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Cholsoon Jang, Shogo Wada, Steven Yang, Bridget Gosis, Xianfeng
Zeng,
Zhaoyue Zhang, Yihui Shen, Gina Lee, Zoltan Arany, Joshua
D. Rabinowitz.

The small intestine shields the liver from fructose-induced
steatosis.

Nature Metabolism, 2020; DOI: 10.1038/s42255-020-0222-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200629120250.htm

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