University of Gothenburg

Hormone removes the pleasure of smoking.

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The hormone GLP-1 is released when we eat and makes us feel full or sated toward the end of the meal.

 GLP-1 receptors are also activated in parts of the brain that are linked to satisfaction or a sense of reward. This indicates the hormone is directly involved in our experience of gratification.

Scientists reason that by blocking these receptors they can prevent smokers from feeling satisfied after a cigarette.

“Without this kind of reward, a smoker will not keep smoking. It can reduce addiction and the risk of a relapse,” says Elisabet Jerlhag, a researcher at the Sahlgrenska Academy of the University of Gothenburg.

Jerlhag and colleagues have investigated this new potential weapon in the battle against smoking.

Smokers require treatment

The ranks of daily, habitual smokers are on the decline but tobacco smoke remains a substantial public health challenge. One in four Norwegians smoke on occasion and the numbers of such “party smokers” are fairly stable.

Even those who are not heavy, daily smokers can find it hard to stub their cigs for good.

“Nicotine is remarkably habit-forming, and many people find it terribly hard to quit smoking. We need to start accepting dependency as a disorder that requires treatment,” says Jerlhag.

Tested on nicotine mice

To test whether GLP-1 regulates gratification, the researchers experimented with another chemical substance, Exendin-4 (Ex4), which imitates GLP-1’s effect on receptors. The substance was administered to a group of lab mice who had been given doses of nicotine.

The researchers then observed the mice’s movement patterns as well as the dopamine releases in their brains.

They found that nicotine made the mice more active, but the addition of Ex4 reduced that activity. However, mice that had not been given nicotine to start with did not experience the mitigating effect of Ex4. Nicotine increased the release of dopamine in their brains, but this was reduced when Ex4 had been given earlier.

The researchers concluded that GLP-1 receptors regulated the effect of nicotine on the reward functions in the brains of mice, and that Ex4 diminished the effect of nicotine.

Same effect on alcohol, amphetamines and cocaine

The researchers point out that other experiments have shown the same mitigating effect of Ex4 with other habit-forming substances such as alcohol, amphetamines and cocaine.

“Because Ex4 also reduced the motivation for consuming sucrose, this could indicate that GLP-1 receptors play a key role in the gratification created by addictive substances and the rewards of natural activities,” they add.

The researchers believe that substances that mimic the GLP-1 hormone should be considered for new prospective treatment regimens to help battle smoking and nicotine addiction.

Developing new medications

This method, which prevents smoking from soothing the nicotine cravings, is different from existing methods for treating habitual tobacco use, such as nicotine patches, or drugs such as bupropion or varenicline.

The hope is that the findings can lead to the development of new medications that mimic GLP-1. These kind of drugs have already been approved for diabetes, so that it should be relatively easy to get the green light to use them to help smokers kick their habit.

“Rewards are a prime reason why we become addicts. So we think medications that work in the same way as GLP-1 can have a positive impact on nicotine dependency. This is a whole new approach,”  Jerlhag says.

Epilepsy Risk for Men Reduced with Exercise.

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Story at-a-glance

  • Men who had a high level of fitness when they were young were 79 percent less likely to develop epilepsy later in life compared to those with low fitness levels
  • Compared to young men with average fitness levels, the high-fitness group was still 36 percent less likely to develop epilepsy
  • Exercise may protect the brain and create a stronger brain reserve, which may reduce epilepsy risk
  • If you have epilepsy, exercising may help to reduce the frequency of seizures.

 

The next time you work out, take a moment to think about all of the wonderful ways it is benefitting your body. And I’m not only talking about your muscles or your six-pack abs… I’m referring to you brain.

Exercise is emerging as a key player in brain health at various stages of life and has been shown to prevent cognitive decline, moderate brain damage caused by drinking and even lower your risk of brain diseases like Alzheimer’s. Now, researchers have uncovered yet another brain benefit of exercise – a reduced risk of epilepsy.

Vigorous Exercise May Reduce Epilepsy Risk by Up to 80 Percent

In a study involving more than 1.1 million men who were followed for an average of 25 years, those who had a high level of fitness when they were young were 79 percent less likely to develop epilepsy later in life compared to those with low fitness levels.1

Compared to young men with average fitness levels, the high-fitness group was still 36 percent less likely to develop epilepsy. This is the first study in humans to reveal that exercise may impact epilepsy risk. One of the study’s researchers noted:2

“Exercise may affect epilepsy risk in two ways. It may protect the brain and create stronger brain reserve, or it may simply be that people who are fit early in life tend to also be fit later in life, which in turn affects disease risk.”

Exercise May Reduce Seizure Frequency in People with Epilepsy

Epilepsy is a neurological disorder involving disturbed nerve cell activity in your brain. This results in seizures that may include a staring spell, confusion, uncontrollable jerking movements and loss of consciousness or awareness. Obviously, this presents risks of falls and injuries that may occur if you have a seizure while driving or even exercising.

For this reason, people with epilepsy have previously been discouraged from participating in physical activity, and this stigma remains today even though medical recommendations have long since changed.

Now, exercise is highly recommended for people with epilepsy, for starters because it helps to reduce stress levels, which can sometimes trigger seizures. In fact, physical activity has been shown to decrease seizure frequency,3 as well as lead to improved cardiovascular and psychological health in people with epilepsy.4

Tips for Exercising if You Have Seizures

If you have epilepsy, make sure you exercise with a buddy or a personal trainer who knows what to do if you have a seizure. A medical alert bracelet can also be worn.

Try to exercise in a safe area, such as a grassy field or on a gym mat, and wear elbow and knee pads. If you’ll be swimming, be sure you wear a life vest and never go swimming alone (a strong swimmer should be with you at all times in case you need help).

If you’ll be exercising on a bicycle, stay away from busy streets (and wear a helmet)… likewise if you’ll be hiking — stick to simpler trails, not those with steep drop-offs or cliffs. If you have epilepsy, you’ll need to take special care during activities that pose a risk of a blow to your head, such as football; if you do engage in such sports be sure to wear a helmet.

Generally speaking, however, you can exercise normally if you have epilepsy, but do use commonsense precautions – avoid getting over-tired or overheated, and avoid exercising when it’s very hot. As an aside, if you have epilepsy, be sure to get your vitamin D levels checked. When epileptic patients improved their vitamin D levels, their seizures were reduced by an average of 40 percent in one study.5

What Else Can Exercise Do for Your Brain?

Along with potentially reducing your risk for epilepsy quite significantly, scientific evidence shows that physical exercise helps you build a brain that not only resists shrinkage, but also increases cognitive abilities.6 In one review of more than 100 studies, both aerobic and resistance training were found to be important for maintaining cognitive and brain health in old age.7 Moderate exercise may even reverse normal brain shrinkage by 2 percent, effectively reversing age-related hippocampus degeneration, which is associated with dementia and poor memory, by one to two years.8

Not to mention, other contributing factors to brain disease caused by the normal aging process may also include a decrease in blood flow to your brain, and the accumulation of environmental toxins in your brain. Exercise can help ameliorate both of these conditions by increasing blood flow to your brain, thereby increasing oxygen supply to your brain and encouraging a more vigorous release and removal of accumulated toxins through better blood circulation.

You’ve Got to Move It… Or You Might Lose It

If you work out religiously for three months, then suddenly stop for an extended period, your muscle tone will definitely suffer. This is one of the more obvious examples that your body is designed for regular exercise, not sporadic or infrequent activity.

Likewise, research suggests that the brain benefits of exercise also quickly fade if your exercise program stops. The silver lining is that the opposite also appears to hold true. While the benefits of exercise might fade fast, they can also be achieved relatively quickly.

Exercising – even briefly – can change your DNA in a way that readies your body for increased muscle strength and fat burning. It also boosts your natural human growth hormone (HGH) production, which is important for maintaining muscle mass as you age. If you’re approaching middle-age or beyond, you might be thinking that it’s too late for you to get in shape, but this is not the case. Remember, you are never too old to start exercising and start reaping the mental and physical benefits that physical activity has to offer.

 

If you have epilepsy and are unable to control the seizures, or have refractory epilepsy – or know someone who is affected – please view the video above, which is my interview with Dr. Thomas Seyfried about the ketogenic diet. The ketogenic diet has been used for managing seizures for quite some time, and is now recognized as an important component for the management of refractory seizures in children. A ketogenic diet calls for eliminating all but non-starchy vegetable carbohydrates, and replacing them with healthy fats and high-quality protein.

Eating this way will help you convert from carb-burning mode to fat burning, as well, so it provides many benefits beyond seizure control. According to Dr. Seyfried, the mechanism by which the ketogenic diet manages seizures is not clear, but the results speak for themselves. You can learn more about the ketogenic diet here.

Want to Boost Your Brainpower? Try This Exercise ‘Prescription’

The more active you stay, the better your brain (and overall health) is likely to be. This includes not only specifically engaging in exercise and other physically demanding activities but also making an effort to sit less. To get all the benefits exercise has to offer, you’ll want to strive for a varied and well-rounded fitness program that incorporates a variety of exercises. I recommend incorporating the following types of exercise into your program:

    • High-Intensity Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercisewith gentle recovery periods. The HIIT approach I personally prefer and recommend is the Peak Fitness method of 30 seconds of maximum effort followed by 90 seconds of recuperation.

I personally modified the number of repetitions from 8 to 6 this year, as it was sometimes just too strenuous for me to do all 8. So by listening to my body and cutting it back to 6 reps, I can now easily tolerate the workout and go full out. You can see a demonstration of Peak Fitness in the video I did.

    • Strength Training: If you want, you can increase the intensity by slowing it down. You need enough repetitions to exhaust your muscles. The weight should be heavy enough that this can be done in fewer than 12 repetitions, yet light enough to do a minimum of four repetitions. It is also important NOT to exercise the same muscle groups every day. They need at least two days of rest to recover, repair and rebuild. For more information about using super slow weight training as a form of HIIT, please see my interview with Dr. Doug McGuff.
    • Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability.

Exercise programs like Pilates, yoga and Foundation Training are great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.

    • Stretching: My favorite type of stretching is Active Isolated Stretching (AIS) developed by Aaron Mattes. With AIS, you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.
    • Non-Exercise Activity: One of the newest recommendations I have is based on information from NASA scientist Dr. Joan Vernikos, who I recently interviewed: simply set a timer when you are sitting and stand up every 10 minutes. I even modify this further by doing jump squats at times in addition to standing up. This will help counteract the dangerous consequences of excessive sitting.

Going to the gym a few times a week for an hour simply isn’t going to counteract hours upon hours of chronic uninterrupted sitting, which essentially mimics a microgravity situation, i.e. you’re not exerting your body against gravity. Only frequent non-exercise movement will do that. The key point is to move and shift position often, when you’re sitting down. Meaning, you want to interrupt your sitting as often as possible.

Fat Cells Feel the Cold, Burn Calories for Heat.

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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

 

 

Cholera is Altering the Human Genome.

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Cholera kills thousands of people a year, but a new study suggests that the human body is fighting back. Researchers have found evidence that the genomes of people in Bangladesh—where the disease is prevalent—have developed ways to combat the disease, a dramatic case of human evolution happening in modern times.

 

Cholera has hitchhiked around the globe, even entering Haiti with UN peacekeepers in 2010, but the disease’s heartland is the Ganges River Delta of India and Bangladesh. It has been killing people there for more than a thousand years. By the time they are 15 years old, half of the children in Bangladesh have been infected with the cholera-causing bacterium, which spreads in contaminated water and food. The microbe can cause torrential diarrhea, and, without treatment, “it can kill you in a matter of hours,” says Elinor Karlsson, a computationalgeneticist at Harvard and co-author of the new study.

The fact that cholera has been around so long, and that it kills children—thus altering the gene pool of a population—led the researchers to suspect that it was exerting evolutionary pressure on the people in the region, as malaria has been shown to do in Africa. Another hint that the microbe drives human evolution, notes Regina LaRocque, a study co-author and infectious disease specialist at Massachusetts General Hospital, Boston, is that many people suffer mild symptoms or don’t get sick at all, suggesting that they have adaptations to counter the bacterium.

To tease out the disease’s evolutionary impact, Karlsson, LaRocque, and their colleagues, including scientists from the International Centre for Diarrhoeal Disease Research in Bangladesh, used a new statistical technique that pinpoints sections of the genome that are under the influence of natural selection. The researchers analyzed DNA from 36 Bangladeshi families and compared it to the genomes of people from northwestern Europe, West Africa, and eastern Asia. Natural selection has left its mark on 305 regions in the genome of the subjects from Bangladesh, the team reveals online today in Science Translational Medicine.

The researchers bolstered the case that cholera was the driving force behind the genomic changes by contrasting DNA from Bangladeshi cholera patients with DNA from other residents of the country who remained healthy despite living in the same house as someone who fell ill with the disease. Individuals who were susceptible to cholera typically carried DNA variants that lie within the region that shows the strongest effect from natural selection.

One category of genes that is evolving in response to cholera, the researchers found, encodes potassium channels that release chloride ions into the intestines. Their involvement makes sense because the toxin spilled by the cholera bacterium spurs such channels to discharge large amounts of chloride, leading to the severe diarrhea that’s characteristic of the disease.

A second category of selected genes helps manage the protein NF- kB, the master controller of inflammation, which is one of the body’s responses to the cholera bacterium. A third category involves genes that adjust the activity of the inflammasome, a protein aggregation inside our cells that detects pathogens and fires up inflammation. However, the researchers don’t know what changes natural selection promotes in these genes to strengthen defenses against the cholera bacterium.

Researchers have identified other examples of infectious diseases driving human evolution, such as malaria in Africa favoring the sickle cell allele, a gene variant that provides resistance to the illness. But they are just starting to search the entire genome for signs of disease effects, and this study is the first to use such methods for cholera.

“I think it’s a great example of the impact infectious diseases have had on human evolution,” says infectious disease specialist William Petri of the University of Virginia School of Medicine in Charlottesville, who wasn’t involved with the study. “It’s ambitious, fairly extensive, and very well done,” adds medical microbiologist Jan Holmgren of the University of Gothenburg in Sweden. One strength of the work is that it flags genes, such as those involved with the inflammasome, that researchers have implicated in other intestinal illnesses such as inflammatory bowel disease, says genetic epidemiologist Priya Duggal of the Johns Hopkins Center for Global Health in Baltimore, Maryland. “Overall, they make a very nice case.”

The findings probably won’t lead to new cholera treatments, says LaRocque, because current measures—which rapidly replace the water and electrolytes patients lose—work very well. “The real issue with cholera,” she says, “is how do we prevent it,” a difficult problem in areas without clean water supplies. But understanding how humans have evolved in response to cholera might help researchers devise more potent vaccines that would provide better protection against this killer, she says.

Source: sciencemag.org