Published in the April issue of the journal Cell Metabolism, the finding could lead to a better understanding of how we utilize fats from the foods we eat.
"We thought that we had figured out how the body digests and uses fats, but we have identified a completely new player in the game," said the study's author Anne Beigneux, assistant investigator at the David Geffen School of Medicine at UCLA.
Digested fats travel to the small intestine, where they are packaged into chylomicrons, which are large, spherical particles filled with triglycerides.
Chylomicrons then travel through the bloodstream and deliver triglycerides to the skeletal muscles and heart — tissues that are hungry for fuel — or to adipose tissue for energy storage. Molecules called proteoglycans, attached to the inside walls of capillaries, wait like baseball players with their mitts open, poised to catch the passing chylomicrons.
Proteoglycans hold the chylomicrons steady while the triglycerides are broken down or hydrolyzed by the enzyme lipoprotein lipase (LpL). The triglyceride breakdown products are then taken up and used by cells.
"Previously we didn't know what molecule in the capillaries facilitated the capture of chylomicrons and facilitated the interaction with lipoprotein lipase," said Dr. Stephen Young, study author and investigator at the David Geffen School of Medicine at UCLA. "We think that we've found the missing piece of the puzzle."
Investigators discovered that a protein called glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) may be the missing link.
Scientists found that mice deficient in GPIHBP1 develop very high triglyceride levels, even on a normal diet, demonstrating that fats in the bloodstream are not readily metabolized in the absence of GPIHBP1.
Laboratory tests confirmed that GPIHBP1-deficient mice had much higher levels of chylomicrons in the bloodstream than normal mice. The GPIHBP1-deficient mice had grossly milky plasma, reflecting very large amounts of triglycerides in the blood.
"These findings indicate a defect in the breakdown of chylomicrons in mice that don't have GPIHBP1," Beigneux said.
Investigators predicted that if GPIHBP1 were involved in the processing of chylomicrons in the bloodstream, then the protein would be made by endothelial cells of capillaries, where the breakdown of triglycerides takes place. Indeed, microscopy showed that GPIHBP1 is expressed highly and exclusively on the endothelial cells of capillaries of heart, adipose tissue and skeletal muscle.
Interestingly, scientists found that this protein was absent from the brain, which mainly uses glucose for energy.
"These differences suggest that endothelial cells may play an active role in regulating the delivery of lipid nutrients to different tissues," Beigneux said.
Experiments with cultured cells revealed that GPIHBP1 binds both chylomicrons and lipoprotein lipase, suggesting GPIHBP1 is a key platform for the processing of chylomicrons.
The next step, according to investigators, will be to determine if GPIHBP1 provides the only binding site for chylomicrons and lipoprotein lipase within capillaries. In addition, investigators would like to define the molecular basis for how GPIHBP1 binds to chylomicron particles.
Rachel Champeau | EurekAlert!
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology