Blocking a protein in liver cells protects against insulin resistance, fatty liver disease
A new multi-institution study led by a team of researchers at the David Geffen School of Medicine demonstrated that blocking a protein called ABCB10 in liver cells protects against high blood sugar and fatty liver disease in obese mice. Furthermore, ABCB10 activity prompted insulin resistance in human liver cells.
The findings are the first to show that ABCB10 transports biliverdin out of the mitochondria - the cell's "energy generating powerhouses." Biliverdin is the precursor of bilirubin, a substance with antioxidant properties. Consequently, ABCB10 transport activity causes an increase in bilirubin synthesis inside liver cells undergoing fatty liver disease.
Non-alcoholic fatty liver disease is closely linked to obesity and other disorders related to insulin resistance and is becoming increasingly common throughout the world, affecting an estimated 100 million people in the United States.
The liver filters everything that people consume and sorts it for the nutrients that will stay in the body or for the toxins that it will expel. The liver is also one of the organs richest in mitochondria - the small organelles in cells that convert food into usable energy through a process called metabolism. Consequently, the mitochondria produce high levels of free radicals, as well as antioxidants to keep these free radicals at healthy levels. Both free radicals and antioxidants play a key role in regulating metabolism and are elevated in insulin resistance and fatty liver disease.
One of these antioxidants is bilirubin, a yellow-bile substance that is released from the breakdown of biliverdin - its green-bile precursor. Bilirubin is produced at high levels in livers from people with fatty liver disease. Both biliverdin and bilirubin are found naturally in the body and released during the breakdown of heme - the deep red iron-containing molecule in red blood cells, which can be seen in the changing color of bruises - from green (biliverdin) to yellow (bilirubin).
Previous research established that mild increases in blood bilirubin content could be associated with protection from metabolic diseases. However, the effects of bilirubin content inside mitochondria and their relationship to fatty liver disease and insulin resistance, remained unknown. This current study shows that increased bilirubin content inside the mitochondria driven by ABCB10 activity is contributing to fatty liver disease.
In the study, the researchers removed the ABCB10 protein selectively from the livers of mice to test whether ABCB10 removal impacted the ability of obese mice to tolerate glucose, if they developed fat in the liver and how well the mitochondria in their livers were working to convert nutrients into usable energy.
In lean mice, the researchers found no difference in metabolism and health when ABCB10 was removed from their livers, while in obese mice they found that removing ABCB10 protected against insulin resistance and fatty liver disease.
Secondly, the researchers measured bilirubin in the mitochondria of liver cells using fluorescent sensors, as well as testing purified ABCB10 to determine what ABCB10 transports. They found that ABCB10 transports biliverdin out of the mitochondria and increases bilirubin production in liver cells, with ABCB10 removal decreasing mitochondrial bilirubin content to levels observed in lean mice.
Thirdly, the researchers found that when they restored bilirubin content in the mitochondria, the benefits on the function of mitochondria resulting from the removal of ABCB10 were reversed.
These findings shed light on the relevance of the association of some genetic ABCB10 variants with insulin resistance in Type 2 diabetes. While still very early to draw any conclusions, these findings could inspire the development of therapies that target ABCB10 or mitochondrial bilirubin in the liver to reverse fatty liver disease in obese individuals.
The study is published in the May 19 issue of Science Translational Medicine.
The senior author of the study is Dr. Marc Liesa and the first author is Dr. Michael Shum, both in the Department of Medicine, Division of Endocrinology; the Department of Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA. Additional study authors include Vincent Gutierrez of the Medical Scientist Training Program (MSTP) at UCLA and Drs.' Thorsten Althoff and Jeff Abramson from the Department of Physiology at UCLA; Drs.' Chitra A. Shintre and Liz Carpenter from the University of Oxford; Alexandra Saxberg, Melissa Martinez and Dr. Maria Zoghbi from the University of California, Merced; as well as researchers from Boston University School of Medicine; and the University of Cincinnati College of Medicine.
UCLA Health media relations: firstname.lastname@example.org
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
So, you thought the problem of false information on social media could not be any worse? Allow us to respectfully offer evidence to the contrary.
Not only is misinformation increasing online, but attempting to correct it politely on Twitter can have negative consequences, leading to even less-accurate tweets and more toxicity from the people being corrected, according to a new study co-authored by a group of MIT scholars.
The study was centered around a Twitter field experiment in which a research team offered polite corrections, complete with ...
Orangutans are closely related to humans. And yet, they are much less sociable than other species of great apes. Previous studies have showed that young orangutans mainly acquire their knowledge and skills from their mothers and other conspecifics. Social learning in orangutans occurs through peering, i.e. sustained observation of other members of the species at close range.
An international team led by the University of Zurich (UZH) has now studied peering behavior in young orangutans at two research stations on the islands of Sumatra and Borneo. The data was collected by researchers from the Department of Anthropology of UZH, the Max Planck Institute of Animal Behavior in Constance, the Universitas Nasional in Jakarta and Leipzig University, ...
Do we have free choice or are our decisions predetermined? Is physical reality local, or does what we do here and now have an immediate influence on events elsewhere? The answers to these questions are sought by physicists in the Bell inequalities. It turns out that free choice and local realism can be skilfully measured and compared. The results obtained reveal surprising relationships of a fundamental and universal nature, going far beyond quantum mechanics itself.
Causality, locality, and free choice are related by a few simple formulas known as Bell's inequalities. The sophisticated experiments in quantum optics over the past few decades have unquestionably proved that these inequalities are broken. Today, physicists are ...
The genome is tightly organised (packaged) within the cell nuclei. This three-dimensional (3D) genome organisation is fundamental, given that it regulates gene expression.
A study led by scientists at the Universitat Autònoma de Barcelona (UAB) now demonstrates using mice models that the 3D organisation of the genome is extremely dynamic during the formation of male germ cells (precursors of spermatozoa) and that alterations in this structure can affect fertility.
The research, published in Nature Communications, describes the 3D genome organisation in germ cells of wild populations of house mice (Mus musculus domesticus) with chromosomal rearrangements, ...
Since they are far more compact than today's accelerators, which can be kilometers long, plasma accelerators are considered as a promising technology for the future. An international research group has now made significant progress in the further development of this approach: With two complementary experiments at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and at the Ludwig-Maximilians-Universität Munich (LMU), the team was able to combine two different plasma technologies for the first time and build a novel hybrid accelerator. The concept could advance accelerator development ...
An international team, led by researchers from Pompeu Fabra University (UPF) in Barcelona, Spain, David Andreu and Rafael Maldonado, has developed a peptides family that allows delta-9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, to fight pain in mice without side effects. The study, published in the Journal of Medicinal Chemistry, was carried out together with researchers from the Autonomous University of Barcelona, ??the University of Barcelona, and the University of Lisbon.
At present, there are two main types of pain relievers prescribed based on the severity of the pain. Nonsteroidal ...
The high-power and long-pulse operation of tokamak will cause excessive particle flux and heat load on the divertor target plate. The surface of the target plate will be subject to intense sputtering, and the thermal load of the target plate will exceed the material/component limit.
The sputtered atoms generated by the damage of the target plate may be transported to the core plasma, degrading the quality of the fusion plasma and increasing the difficulty of plasma stability control.
Recently, the EAST group of Institute of Plasma Physics, Hefei Institutes of Physical Science (HFIPS), reported their new findings about the influence of different impurity gases ...
"Pretty" parrots are more likely to be snatched up for Indonesia's illegal wildlife trade, a new study reveals.
The findings not only expose the key drivers behind the country's illegal trade in these birds, but offer lessons for the potential emergence and spread of infectious diseases that jump from animals to humans - like COVID-19 and avian flu.
The study, involving researchers from The Australian National University (ANU), analysed two decades worth of data on the illegal trade of parrots in Southeast Asia.
The researchers found some key reasons parrots ...
E-scooters as a new micro-mobility service: SMART researchers explore the potential of e-scooter sharing as a replacement for short-distance transit in Singapore
SMART researchers found that e-scooters are not only a last-mile solution to complement transit services, but also provide a mobility service for short-distance transit trips
- Through a stated preference survey and mixed logit models, SMART researchers found that fare, transit transfer, and transit walking distance are significant factors driving the use of e-scooters as an alternative means of transit. The uncertainty is higher in predicting e-scooter usage preferences of male, young and high-income ...
Tsukuba, Japan - Warm, dry wind events blowing down from mountain slopes, called foehns, are a meteorological phenomenon typically associated with the European Alps or the Rocky Mountains of North America. However, in recent decades, foehn winds in Japan have caused record-breaking hazardous warm weather events, bringing renewed interest in the behavior of these winds in this part of the world.
In a new study published in the International Journal of Climatology, a research team led by the University of Tsukuba has presented the first comprehensive climatological study of Japan's south foehn, a windstorm that originates from the Backbone Mountain Range and is observed along the coast of the Sea of Japan, including in the Toyama ...
LAST 30 PRESS RELEASES:
[Press-News.org] Blocking a protein in liver cells protects against insulin resistance, fatty liver disease