Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

Blocking Fructose Transport Prevents Fatty Liver Disease in Mouse Model

By BiotechDaily International staff writers
Posted on 17 Jun 2014
Image: The transporter GLUT8 (green) is in the outer membrane of liver cells. In mice, blocking GLUT8 stops fructose from entering the liver and protects against nonalcoholic fatty liver disease. The liver cell nuclei are shown in blue (Photo courtesy of Dr. Brian J. DeBosch, Washington University School of Medicine).
Image: The transporter GLUT8 (green) is in the outer membrane of liver cells. In mice, blocking GLUT8 stops fructose from entering the liver and protects against nonalcoholic fatty liver disease. The liver cell nuclei are shown in blue (Photo courtesy of Dr. Brian J. DeBosch, Washington University School of Medicine).
A recent paper showed that blocking the action of the facilitative glucose and fructose transporter enzyme GLUT8 (Slc2A8 or solute carrier family 2 (facilitated glucose transporter) member 8) could prevent nonalcoholic fatty liver disease (NAFLD) in cultured mouse liver tissues.

NAFLD is one of the world's most common liver diseases, and it is considered to be the hepatic manifestation of the metabolic syndrome, which is characterized by obesity, elevated blood sugar, and high blood pressure.

Investigators at Washington University School of Medicine (St. Louis, MO, USA) have been concentrating on the molecular factors regulating fructose transport, since excess dietary fructose causes both metabolic syndrome and NAFLD in rodents and humans. They previously demonstrated that female mice lacking GLUT8 exhibited impaired first-pass hepatic fructose metabolism, suggesting that fructose transport into the hepatocyte, the primary site of fructose metabolism, was in part mediated by GLUT8. In the current study, they tested the hypothesis that GLUT8 was required for hepatocyte fructose uptake and for the development of fructose-induced NAFLD.

The investigators reported in the April 18, 2014, issue of the Journal of Biological Chemistry that GLUT8 was a cell surface-localized transporter and that GLUT8 overexpression or GLUT8 siRNA-mediated gene silencing significantly induced and blocked radiolabeled fructose uptake in cultured hepatocytes. Furthermore, they presented evidence confirming diminished fructose uptake and de novo lipid synthesis in fructose-challenged GLUT8-deficient hepatocytes. Finally, livers from long term high-fructose diet-fed GLUT8-deficient mice were found to exhibit attenuated fructose-induced hepatic triglyceride and cholesterol accumulation without changes in hepatocyte insulin-stimulated Akt phosphorylation. Akt, also known as protein kinase B, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. GLUT8 was thus essential for hepatocyte fructose transport and fructose-induced accumulation of fats in the liver.

“We showed that GLUT8 is required for fructose to get into the liver,” said first author Dr. Brian J. DeBosch, clinical fellow in pediatric gastroenterology at Washington University School of Medicine. “If you take away or block this transporter in mice, they no longer get diet-induced fatty liver disease.”

“Fatty liver disease is a major topic of research right now,” said Dr. DeBosch. “There are competing hypotheses about the origins of metabolic syndrome. One of these hypotheses is that insulin resistance begins to develop in the liver first. The thought is if we can prevent the liver from becoming unhealthy to begin with, maybe we can block the entire process from moving forward.”

Related Links:

Washington University School of Medicine



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: The European Commission has approved the use of Avastin combined with chemotherapy as a treatment for women with recurrent ovarian cancer (Photo courtesy of Genentech).

Drug for Treatment of Platinum Resistant Recurrent Ovarian Cancer Approved for Use in Europe

For the first time in more than 15 years the European Commission (EC) has approved a new therapeutic option for the most difficult to treat form of ovarian cancer. Ovarian cancer causes more deaths... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel
Image: The DrySyn MULTI converts any standard hotplate stirrer into a high performance reaction block (Photo courtesy of Asynt).

New Reaction Vessel Heating System Is Cleaner and Safer

Biotech and other life science researchers can create a safer, cleaner, and more efficient working environment in their laboratories by switching from oil bath-based heating of reaction vessels to a new... Read more

Business

view channel

Global Computational Biology Sector Expected to Reach over USD 4 Billion by 2020

The global market for computational biology is expected to reach USD 4.285 billion by 2020 growing at a compound annual growth rate (CAGR) of 21.1%, according to new market research. Steady surge in the usage and application of computational biology for bioinformatics R&D programs designed for sequencing genomes... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.