This nutrient sensing pathway, which is described in the current on-line issue of Cell Metabolism, may also have implications for the health benefits of polyphenols containing foods against fatty liver, hyperlipidemia, and atherosclerosis associated with obesity and type 2 diabetes.
Although it is well known that elevated serum cholesterol and triglyceride levels and fatty liver are caused by increased hepatic lipid synthesis and/or decreased lipid clearance in patients with obesity and diabetes, the underlying mechanistic pathways of these changes remains unknown.
The master regulators of lipid metabolism that were studied are called AMPK and SREBP. The researchers used a molecular biology approach, cell culture system and animal models to indicate that dysregulation of AMPK, an energy sensor, and SREBP, a protein that is important regulator for lipid biosynthesis, are affected in obesity. Mice fed a diet with high fat and high sucrose became obese and had insulin resistance and elevated circulating levels of cholesterol and triglyceride which led to accelerated atherosclerosis. In contrast, dietary supplementation with S17834, a polyphenol, significantly improved the metabolic disorder, lipid levels and atherosclerosis.
“Our findings suggest that AMPK suppression and SREBP activation are a root cause of fatty liver and hyperlipidemia in type 2 diabetes and its associated vascular complications such as atherosclerosis,” said senior author Mengwei Zang, MD, PhD, an assistant professor of medicine at BUSM.
According to the researchers the potential health benefits of polyphenols have been gaining increasing interest. “In our studies, AMPK is potently and persistently activated by polyphenols including the natural compound resveratrol, which is present in red wine, grapes and green tea, as well as the synthetic polyphenol S17834, which is a drug candidate provided by Servier Pharmaceutical Company,” explained Zang.
“AMPK directly suppresses SREBP via its phosphorylation, inhibiting the activity of its target lipogenic enzymes in the liver, and accounting for the protective effects of the polyphenols on fatty liver, blood lipids and diabetic atherosclerosis,” she added.
The researchers believe these findings may lead to the development of new drugs that could stop or slow diabetes progression or improve current treatments.
Gina DiGravio | EurekAlert!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy