Studying mice, researchers have found a way to prevent nonalcoholic fatty liver disease, the most common cause of chronic liver disease worldwide.
Blocking a path that delivers dietary fructose to the liver prevented mice from developing the condition, according to investigators at Washington University School of Medicine in St. Louis.
The study appears in a recent issue of The Journal of Biological Chemistry.
In people, nonalcoholic fatty liver disease often accompanies obesity, elevated blood sugar, high blood pressure and other markers of metabolic syndrome. Some estimate as many as 1 billion people worldwide have fatty liver disease, though some may not realize it.
“Fatty liver disease is a major topic of research right now,” said first author Brian J. DeBosch, MD, PhD, clinical fellow in pediatric gastroenterology. “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.”
The research team, led by Kelle H. Moley, MD, the James P. Crane Professor of Obstetrics and Gynecology, showed that a molecule called GLUT8 carries large amounts of fructose into liver cells. Fructose is a type of sugar found in many foods. It is present naturally in fruit and is added to soft drinks and myriad other products in the form of high-fructose corn syrup.
Scientists have known that fructose is processed in the liver and stored there as fat in the form of triglycerides. In this study, researchers showed that blocking or eliminating GLUT8 in mice reduced the amount of fructose entering the organ and appeared to prevent the development of fatty livers. Mice with GLUT8 deficiency also appeared to burn liver fat at a faster rate than control mice.
“We showed that GLUT8 is required for fructose to get into the liver,” DeBosch said. “If you take away or block this transporter in mice, they no longer get diet-induced fatty liver disease.”
The researchers also saw differences between male and female mice in the degree to which they were protected from fatty livers and in whole-body metabolism. Male mice fed a high-fructose diet while deficient in GLUT8 still had evidence of fatty liver disease, but whole-body metabolism was healthy. They showed no evidence of metabolic syndrome in the rest of the body. Females fed fructose while lacking GLUT8, in contrast, had healthy looking livers but exhibited more evidence of whole-body metabolic syndrome.
“If the fructose doesn’t go into the liver, it may go to peripheral tissues,” DeBosch said. “Female mice with a GLUT8 deficiency had increased body fat. They also had increased circulating triglycerides and cholesterol.
“So the liver is healthier in female rodents, but you could argue that the whole body has worse overall metabolic syndrome,” he said. “This supports the idea of the liver acting as a sort of sink for processing fructose. The liver protects the whole body, but it may do so at its own expense.”
While DeBosch said future therapeutics might be able to target GLUT8 to block fructose from entering the liver, more work must be done to understand how this would impact the rest of the body.
“In a perfect world, it would be good if we could figure out a way to direct fructose to tissues in which you’re more likely to burn it than store it, such as in skeletal muscle,” he said.
In the meantime, DeBosch advises his pediatric patients, many of whom are overweight or obese, to avoid fructose, especially sugar-sweetened drinks, and to find ways to increase physical activity.
This work was supported by the Pediatric Scientist Development Program and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (NIH). Grant numbers K12HD000850-29, DDRCC P30 DK52574, R01 DK078187, and R01HD040390-07. The Washington University Mouse Phenotyping Core is supported by Diabetes Research and Training Center Grant P60 DK020579.
DeBosch BJ, Chen Z, Saben JL, Finck BN, Moley KH. Glucose transporter 8 (GLUT8) mediates fructose-induced de novo lipogenesis and macrosteatosis. The Journal of Biological Chemistry. April 2014.Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
Julia Evangelou Strait | Eurek Alert!
New mechanisms uncovered explaining frost tolerance in plants
26.09.2016 | Technische Universität München
Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.
In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...
Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
23.09.2016 | Event News
20.09.2016 | Event News
16.09.2016 | Event News
26.09.2016 | Physics and Astronomy
26.09.2016 | Physics and Astronomy
26.09.2016 | Life Sciences