ETH Zurich

Cholesterol-lowering drugs reduce brown adipose tissue

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Cholesterol-lowering drugs reduce brown adipose tissue
Statins reduce brown adipose tissue.

ETH Zurich scientists have shown that statins, one of the most commonly prescribed classes of pharmaceuticals, reduce beneficial brown adipose tissue. But this is no reason to demonise these drugs, the researchers insist.

A certain proportion of the adult population has not only white adipose (or fatty) tissue, but also the brown kind. This brown adipose tissue helps to convert sugar and fat into heat. People with brown adipose tissue are better at regulating their body temperature in the winter, and are less likely to suffer from excess weight or diabetes.

An international team of researchers led by Christian Wolfrum, Professor for Translational Nutritional Biology at ETH Zurich, has now discovered that the class of pharmaceuticals reduces the formation of brown adipose tissue. Statins are prescribed as a way to reduce the risk of a heart attack since they reduce in the blood. They are among the most commonly prescribed drugs worldwide.

Of mice and men

Wolfrum and his colleagues have been researching brown adipose tissue for many years. They looked into the question of how “bad” white fat cells, which form the layer of fat under our skin, become “good” brown fat cells. Having conducted cell culture experiments, they found out that the biochemical pathway responsible for producing cholesterol plays a central role in this transformation. They also discovered that the key molecule regulating the transformation is the metabolite geranylgeranyl pyrophosphate.

Earlier studies showed that the cholesterol biochemical pathway is also central to the functioning of statins; one of their effects is to reduce the production of geranylgeranyl pyrophosphate. This is why the researchers wanted to know whether statins also impact the formation of brown adipose tissue. And indeed they do, as the scientists have now shown in studies on mice and humans.

One thing the researchers did was study positron emission tomography scans of 8,500 patients at the University Hospital Zurich. This let them determine whether the person had brown adipose tissue. It was also known whether the patients were taking statins. Evaluating the scans shows that 6 percent of those not taking the medication had brown adipose tissue, but this tissue type was present in only a little over 1 percent of those who were taking statins.

The researchers conducted a separate clinical study of 16 people at the University Hospitals of Basel and Zurich to demonstrate that statins reduce the activity of brown tissue.

“Incredibly important medications”

Although the study demonstrated that statins have a , Wolfrum warns against talking them down. “We also have to consider that statins are incredibly important as a way to prevent cardiovascular disease. They save millions of lives around the world, and they are prescribed for a very good reason,” he says.

However, statins also have another : in high doses, they slightly increase some people’s risk of developing diabetes – as has been shown in other studies. “It’s possible that these two effects – the reduction in and the slightly increased risk of diabetes – are related,” Wolfrum says, adding that this question requires further research.

But Wolfrum stresses that even if such a link were established, that would be no reason to demonise statins. Rather, it would become imperative to conduct further research into the mechanisms behind this and find out which patients are affected. It might then be possible to take a personalised medicine approach and continue to recommend statins to most people, while proposing alternative therapies for a small group of patients.

Sound Waves Levitate and Move Objects.

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A new approach to contact-free manipulation could be used to combine lab samples–and prevent contamination

Water droplets, coffee granules, fragments of polystyrene and even a toothpick are among the items that have been flying around in a Swiss laboratory lately — all of them kept in the air by sound waves. The device that achieves this acoustic levitation is the first to be capable of handling several objects simultaneously. It is described today in theProceedings of the National Academy of Sciences.

Typically, levitation techniques make use of electromagnetism; magnetic forces have even been used to levitate frogs. It has long been known that sound waves could counter gravity, too, but so far the method has lacked practical application because it could do little more than keep an object in place.

To also move and manipulate levitating objects, Dimos Poulikakos, a mechanical engineer at the Swiss Federal Institute of Technology (ETH) in Zurich, and his colleagues built sound-making platforms using piezoelectric crystals, which shrink or stretch depending on the voltage applied to them. Each platform is the size of a pinky nail.

The platforms emit sound waves which move upward until they reach surface lying above, where they bounce back. When the downward-moving reflected waves overlap with the upward-moving source waves, the two ‘cancel out’ in the middle, at so-called node points. Objects placed there remain stuck in place because of the pressure of sound waves coming from both directions.

By adjusting the position of the nodes, the researchers can tow the objects between platforms. The platforms can be arranged in different ways to adapt to various experiments. In one demonstration involving a T-shaped array of platforms, the researchers joined two droplets introduced at separate locations then deposited the combined droplet at a third location.

Hands-free reactions
The system could be used to combine chemical reactants without the contamination that can result from contact with the surface of a container. Sound waves are already used in the pharmaceutical industry to obtain accurate results during drug screening. Yet Poulikakos’s method is the first to offer the possibility of precisely controlling several items simultaneously.

Poulikakos suggests that the system could be used to safely try out hazardous chemical reactions. “We had fun demonstrating the idea by colliding a lump of sodium with some water, which is obviously an aggressive reaction,” he says.

Peter Christianen, a physicist who works on electromagnetic levitation at Radboud University in Nijmegen, the Netherlands, says that he’s impressed with the invention. “I really like it; this is a very versatile platform — almost anything you want to manipulate, you can.”

Source: Scientific American

 

Like Father, Like Son.

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A 10-year-old boy spends his summer vacation helping his chemist dad solve the structure of complicated materials.

Chemist Sven Hovmöller of Stockholm University had been trying for nearly a decade to determine the structures of materials known as quasicrystals and their nearly identical approximants. Thought to be physically impossible until some 30 years ago, quasicrystals are aperiodic structures—meaning they don’t display the rigidly repeating patterns characteristic of crystals like sodium chloride, for example. Since their discovery in the lab, physicists had been working tirelessly to better understand the structure of quasicrystals. But because the existence of such materials was doubted for so long, computer programs currently used to interpret imaging data aren’t equipped to analyze the aperiodic structures.

Hovmöller has worked on and off in the field of quasicrystals for more than 25 years, focusing primarily on the aluminum-cobalt-nickel (Al-Co-Ni) system. Like other quasicrystal researchers, he studied not the elusive materials themselves but their approximants, which differ in atom placement by only 1 or 2 percent and have more tractable patterns of atomic arrangement. Hovmöller’s interest in quasicrystals was piqued when he saw a conference poster displaying an electron diffraction pattern of one of the Al-Co-Ni approximants. The image was “so beautiful, so clear, [that] it should be possible to solve it,” recalls Hovmöller, who immediately invited Markus Döblinger, the student who made the poster, to do a postdoc in his lab.

But after months of further electron microscopy studies, the duo couldn’t seem to solve the structure. “Not only him and me, but other people also involved, tried so hard, but we didn’t get anywhere,” Hovmöller recalls. “It was extremely annoying.”

The image was so beautiful, so clear, that it should be possible to solve it.
—Sven Hovmöller, Stockholm University

Döblinger eventually moved on to the University of Munich, but Hovmöller couldn’t let the idea go. “Every year, once or twice, I [tried] to solve these things, and I just couldn’t.” Then, last summer, he had a seemingly off-the-wall idea. He’d enlist the aid of his 10-year-old son, Linus. “I thought, He’s a smart guy; maybe he could help me,” Hovmöller says.

The father-and-son team sat at the kitchen table for 2 days, poring over the dozens of electron microscopy images Döblinger had generated, as well as some electron diffraction data, which provides more precise information on the materials’ atomic positions. Hovmöller would explain to Linus what he was thinking about how the images all fit together, and when Linus didn’t understand something, he’d interrupt his father to ask. This made Hovmöller realize that he was rushing to conclusions. When he slowed down to clear up Linus’s confusion, he’d get new ideas. “In 2 days, we solved four new structures.”

They published their findings in a special issue of Philosophical Transactions of the Royal Society A honoring the 85th birthday of Alan Mackay, who had predicted the existence of quasicrystals before they were identified in 1982. Linus was listed as a coauthor on the paper (370:2949-59, 2012).

“A kid [who] is clever and good at spatial things might well come up with a solution to a problem like that,” says surface physicist Renee Diehl of Penn State University. “I think there’s probably a lot of potential in 10-year-old kids that we’re not tapping.”

And in fact, Linus isn’t as unlikely a character as one might expect in the field of quasicrystals. “There have been a lot of highly creative and unusual people associated with the field,” says Carnegie Mellon University theoretical physicist Mike Widom. Amateur mathematician Robert Ammann, for example, made several significant contributions to quasicrystal theory before the crystals were even proven to exist. Others have pointed to the links between quasicrystals and art, such as aperiodic tilings and mosaics found in Persia. There’s even a company, called Zometool, that manufactures toys used to model quasicrystalline shapes, Widom notes. “The field is quite rich … [in] unusual personalities,” he says. “This boy is in the tradition of the field attracting some nontraditional scientists.”

But all the structures of the Al-Co-Ni quasicrystal and its approximants aren’t exactly solved. “What Sven Hovmöller did is quite nice,” says Walter Steurer of the Laboratory of Crystallography at ETH Zurich, but his methods are qualitative. Thus, Hovmöller and Linus merely mapped out some of the repeating motifs in four of the approximant structures, but “did not publish any atomic coordinates.” The precise locations of some of the crystals’ atoms have yet to be pinpointed.

“A lot of the interesting controversy in the field of quasicrystals has to do with fairly fine details,” which are critically important to understanding the materials’ true structures, Widom says. “You can know where 90 percent of the atoms are, but still not really know the structure because a minority of the atoms are doing interesting and crucial things. . . . What [Hovmöller and Linus] give us is a good starting point for future structure refinement.”

But if someone eventually solves the true structure of the Al-Co-Ni quasicrystal or its approximants, it won’t be Linus. “He’s refused” to work on the remaining structures, Hovmöller says with a laugh. “He’s still a little bit tired” from the last bout of structure solving.

http://www.sciencedaily.com