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.

Don’t want to put on weight as you get older? Try sweet chili peppers and cold spells.


Don’t want to put on weight as you get older? Try sweet chili peppers and cold spells .

Scientists say exposure to moderately cold temperatures and a chemical found in chilies have been shown to boost levels of ‘brown fats’ linked to staving off weight gain.

Scientists have discovered that prolonged exposure to cold temperatures and eating chili peppers can help to prevent people putting on weight as they get older.

In a ground-breaking study from Japan, it has been shown that both cold and a chemical found in the peppers have similar effects in building up levels of BAT (brown adipose tissue), which helps regulate the way the body expends energy.

BAT is a kind of tissue that exists in all babies, found around the neck and chest, but which gradually breaks down as adults get older. This rate varies between people, and previous studies have proven there is a link between BAT levels dropping off and age-related weight-gain setting in.

This is the first time anyone has been able to prove BAT levels can be made to recover once lost. Scientists exposed test subjects to moderately low temperatures, around 17°C, for two hours every day over six weeks.

When compared to a control group that went about their lives as normal, those subjected to cold showed increased levels of BAT – and also lost around 5 per cent of their body fat.

While this might seem a fairly obvious outcome as the test subjects’ bodies work harder to keep warm, what was really surprising was the similar effect on BAT of consuming “capsinoids”, found predominantly in sweet chili peppers.

Capsinoids have been shown to activate temperature sensors in the gut – similar to the way hot-tasting chilies impact sensors in the mouth.

Those studied who ate large quantities of peppers were also seen to experience increases in BAT tissue – though they didn’t, yet, lose body fat. Researchers speculated that a longer study would likely show genuine weight loss to go with the recovery of BAT.

Lead researcher and report author Takeshi Yoneshiro, from the Hokkaido University Graduate School of Medicine in Japan, said: “Our results showed that human BAT could be recruited even in individuals who had lost BAT, thereby contributing to body fat reduction. This is the first report of successful recruitment of BAT leading to reduced body fat in humans.”

He added that capsinoids appear to induce so-called “brown fat” in the same way as cold by “capturing” the same cellular system that the body’s nervous system uses to increase heat production.

Source: Journal of Clinical Investigation.

Fat Cells Feel the Cold, Burn Calories for Heat.


Transforming fat cells into calorie-burning machines may sound like the ultimate form of weight control, but the idea is not as far-fetched as it sounds. Unexpectedly, some fat cells directly sense dropping temperatures and release their energy as heat, according to a new study; that ability might be harnessed to treat obesity and diabetes, researchers suggest.

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Fat is known to help protect animals from the cold—and not only by acting as insulation. In the early 1990s, scientists studying mice discovered that cold temperatures trigger certain fat cells, called brown adipose tissue, to release stored energy in the form of heat—to burn calories, in other words. Researchers have always assumed this mechanism was an indirect response to the physiological stress of cold temperatures, explains cell biologist Bruce Spiegelman of Harvard Medical School, Boston. The activation of brown fat seems to start with sensory neurons throughout the body informing the brain of a drop in temperature. In response the brain sends out norepinephrine, the chief chemical messenger of the sympathetic nervous system, which mobilizes the body to cope with many situations. In experimental animals, stimulating norepinephrine receptors triggered brown adipose tissue to release its energy and generate heat, while animals bred to be missing these receptors were unable to mount the same fat cell response.

People also have brown adipose tissue that generates heat when the body is cold. And unlike white fat, which builds up around the abdomen and contributes to many disorders including heart disease and diabetes, this brown fat is found in higher proportions in leaner people and seems to actively protect against diabetes.

In brown fat, the heat-generating process depends on a protein called UCP1; the protein is also thought to be central in brown fat’s ability to prevent diabetes. Researchers are now exploring ways of activating this molecular pathway. But in trying to figure out exactly how fat cells respond to the body being cold, Spiegelman and colleagues discovered that plain old “white” fat cells have a few surprises left. In a study appearing online today in the Proceedings of the National Academy of Sciences, the researchers exposed various kinds of fat cells to cold temperatures directly. “We were a little surprised that no one had tried this before,” Spiegelman says.

The researchers cooled several types of lab-grown human fat cells—brown, white and “beige” (white adipose tissue with some brown cells mixed in)—to temperatures between 27˚ and 39˚C for four hours, eight hours, or up to ten days. White fat cells and beige cells responded to cooling in dramatic fashion. In these cells, levels of the UCP1 were doubled by 8 hours after the treatment. The change in UCP1 also proved to be reversible: Its levels returned to normal once the cells’ temperature was lowered to 37 degrees. But in brown fat cells, no induction of the protein was observed, indicating that cold temperatures don’t mobilize these cells by flipping this particular switch.

The researchers also found that white fat cells obtained from mice lacking receptors for norepinephrine were still able to respond to cooling by turning on UCP1—showing that the heat-generating pathway is both specific to those fat cells and independent of the sympathetic nervous system .

The finding won’t lead to an antifat pill any time soon, Spiegelman says, but it does give scientists new avenues to explore. “It’s a piece of the basic science, adding to an evolving awareness that fat cells have many lives that we never knew about. Now we know they can sense temperature directly. The next question is, how do they do it, and can that ability be manipulated?”

“The paper is filling in an emerging picture that adipose tissue can be a more flexible, adaptive organ than we once thought,” says Sven Enerbäck, a physician and adipose tissue researcher at the University of Gothenburg in Sweden. “The finding raises the question of whether this new pathway has widespread effects on the animal as a whole.”

Finding that white fat cells directly detect and react to cold is a surprising development, notes cell biologist Peter Tontonoz of the University of California, Los Angeles, because it shows that the sympathetic nervous system isn’t the whole story when it comes to heat generation by adipose tissue. He’s curious whether the heat-generating pathway in white fat is a routine part of everyday temperature regulation. “Even if it isn’t,” he adds, “it could still be targeted by small molecules or other drugs.”

Source: sciencemag.org