MIT researcher reports oxygen free radicals don’t cause aging

MIT researchers reported in Nature results that counter the idea that oxygen free radicals cause aging, instead that calorie restriction prolongs life because it increases respiration, not because it decreases oxygen free radicals.

MIT biologist Leonard Guarente believes “the conventional wisdom on oxygen radicals is dead wrong. Our results (in yeast) are contrary to the frequent suggestion that calorie restriction functions by slowing metabolism and thereby slowing the generation of free radicals.”

Guarente, who is working on a book on aging to be published this fall, discovered in 2000 that calorie restriction activates the silenced information regulator (SIR2) gene, which has the apparent ability to slow aging. This gene makes a protein called Sir2, which Guarente has shown is integrally tied to extending life span in yeast and in the roundworm. Humans carry a similar gene.

Rather than a slower metabolism leading to a slower rate of respiration, it turns out that respiration in yeast cells under calorie restriction goes up, not down. “The increase in anti-oxidant enzymes that is reported to occur during calorie restriction in animals may be a result of an increase in respiration rather than a cause of the observed longevity,” Guarente said.

“A high respiration rate is intimately connected with calorie restriction in yeast,” he said. “A high respiration rate activates SIR2. When respiration goes up, NAD (nicotinamide adenine dinucleotide, a co-enzyme that activates SIR2) goes up and SIR2 goes up. When SIR2 goes up, longevity happens.”

A MIRACLE PILL

The prospect of a possible future drug seems too good to be true: Lose weight and live longer. Guarente’s aim is just such a drug.

Calorie restriction extends life span in a wide spectrum of organisms. It is the only regimen known to lengthen the life span of mammals such as mice and rats. One conventional theory for why this works is that to conserve energy and live within the means of limited food intake, the organism’s metabolism slows down.

Because a 30 percent reduction in calories is too difficult for most people to maintain, Guarente hopes to find the knowledge that would allow a pharmacological “trick” to make the organism think that it is calorie-restricted even when it is not. The hoped-for result is that this will trigger longevity.

DIVERTING ENERGY

When a yeast cell metabolizes food, the process can lead to respiration or fermentation, both of which supply the cell with energy.
When there is plenty of food available, yeast cells prefer to use food for fermentation. When food is scarce, the cell opts for respiration. Guarente found that this metabolic shift toward respiration increases SIR2’s activity and thus life span, just as calorie restriction does.

In mammals, excess carbon is used to make fatty acids and store carbohydrates. If there is a way to mimic this metabolic shift in humans, it would mean that more food would be used for respiration and less would be stored as fat. The result? We could live longer and be thinner.

THE CULPRIT BEHIND AGING

Studies have suggested that calorie restriction slows aging primarily because it decreases oxygen free radicals. Oxygen free radicals are byproducts of oxidation, the body’s process of turning oxygen into energy.

Free radicals are thought to be toxic, causing damage to DNA and cells. Although antioxidants “clean up” free radicals, this process becomes more inefficient as we age. Many scientists speculate that free radical damage is the primary culprit behind age-related diseases and the symptoms of aging.

Contrary to these previous findings, Guarente says in the current paper that oxygen free radicals do not limit the reproductive life span of yeast and are not central to the extension of life span by calorie restriction.

Co-authors for the paper are Su-Ju Lin, Matt Kaeberlein, Pierre-Antoine Defossez of the MIT Department of Biology; biology graduate student Alex A. Andalis and MIT Professor of Biology Gerald Fink of the Whitehead Institute for Biomedical Research and Lori A. Sturtz and Valerie C. Culotta of the Johns Hopkins School of Public Health.
This work is supported by the National Institutes of Health, the Ellison Medical Foundation, the Seaver Institute and the Howard and Linda Stern Fund.

——————————————————————–

Article adapted by MD Only from original press release.

——————————————————————–

Contact: Deborah Halber
MIT News.

Researher’s Discover Food Related Clock in the Brain

In investigating the intricacies of the body’s biological rhythms, scientists at Beth Israel Deaconess Medical Center (BIDMC) have discovered the existence of a “food-related clock” which can supersede the “light-based” master clock that serves as the body’s primary timekeeper. The findings, which appear in the May 23 issue of the journal Science, help explain how animals adapt their circadian rhythms in order to avoid starvation, and suggest that by adjusting eating schedules, humans too can better cope with changes in time zones and nighttime schedules that leave them feeling groggy and jet-lagged.

“For a small mammal, finding food on a daily basis is a critical mission,” explains the study’s senior author Clifford Saper, MD, PhD, Chairman of the Department of Neurology at BIDMC and James Jackson Putnam Professor of Neurology at Harvard Medical School. “Even a few days of starvation is a common threat in natural environments and may result in the animal’s death.”

The suprachiasmatic nucleus (SCN), a group of cells in the brain’s hypothalamus, serves as the body’s primary biological clock. The SCN receives signals about the light-dark cycle through the visual system, and passes that information along to another cell group in the hypothalamus known as the dorsomedial nucleus (DMH). The DMH then organizes sleep-wake cycles, as well as cycles of activity, feeding and hormones.

“When food is readily available,” explains Saper, “this system works extremely well. Light signals from the retina help establish the animals’ circadian rhythms to the standard day-night cycle.” But, if food is not available during the normal wake period, animals need to be able to adapt to food that is available when they are ordinarily asleep.

In order to survive, animals appear to have developed a secondary “food-related” master clock. “This new timepiece enables animals to switch their sleep and wake schedules in order to maximize their opportunity of finding food,” notes Saper, who together with lead author Patrick Fuller, PhD, HMS Instructor in Neurology and coauthor Jun Lu, MD, PhD, HMS Assistant Professor of Neurology, set out to determine exactly where this clock was located.

“In addition to the oscillator cells in the SCN, there are other oscillator cells in the brain as well as in peripheral tissues like the stomach and liver that contribute to the development of animals’ food-based circadian rhythms,” says Saper. “Dissecting this large intertwined system posed a challenge.”

To overcome this obstacle, the authors used a genetically arrhythmic mouse in which one of the key genes for the biological clock, BMAL1, was disabled. They next placed the gene for BMAL1 into a viral vector which enabled them to restore a functional biological clock to only one spot in the brain at a time. Through this step-by-step analysis, the authors uncovered the feeding entrained clock in the DMH.

“We discovered that a single cycle of starvation followed by refeeding turns on the clock, so that it effectively overrides the suprachiasmatic nucleus and hijacks all of the circadian rhythms onto a new time zone that corresponds with food availability,” says Saper. And, he adds, the implications for travelers and shift workers are promising.

“Modern day humans may be able to use these findings in an adaptive way. If, for example, you are traveling from the U.S. to Japan, you are forced to adjust to an 11-hour time difference,” he notes. “Because the body’s biological clock can only shift a small amount each day, it takes the average person about a week to adjust to the new time zone. And, by then, it’s often time to turn around and come home.”

But, he adds, by adapting eating schedules, a traveler might be able to engage his second “feeding” clock and adjust more quickly to the new time zone.

“A period of fasting with no food at all for about 16 hours is enough to engage this new clock,” says Saper. “So, in this case, simply avoiding any food on the plane, and then eating as soon as you land, should help you to adjust – and avoid some of the uncomfortable feelings of jet lag.”

———————————–
Article adapted by MD Only from original press release.
———————————–
Contact: Bonnie Prescott>
Beth Israel Deaconess Medical Center

Fat Breakdown is affected by nutrition

Scientists have shown that when either lean or obese individuals exercise after eating a high fat meal, their fats are broken down and oxidized in skeletal muscle, making them healthier. These results show for the first time how a high fat diet and exercise stimulate the breakdown of fats and may help design ways to reduce excessive fat in the body.

Fat is broken down inside fat cells to generate energy by a process called lipolysis. The resulting fatty acids are released into the bloodstream and carried to tissues that require energy. In obese individuals, too much fat accumulates, compromising lipolysis, but the details of how this happens are not well understood. Also, obese individuals can show altered responsiveness to the stress hormones epinephrine and norepinephrine in their subcutaneous fat.

Max Lafontan and colleagues investigated how fat is broken down in both lean and obese subjects who exercised after either fasting or eating a high-fat diet. They noticed that after eating a high-fat diet, fats were broken down in both lean and obese individuals. Under fasting conditions, the breakdown of fats was more pronounced in the lean subjects, but the high fat meal enhanced lipolysis in the obese subjects.

The scientists also studied the effects of long-chain fatty acids (LCFAs) – which are found in high fat diet – on cultured fat cells. They noticed that LCFAs increase lipolysis when it is induced by epinephrine, one of the hormones known to stimulate lipolysis.

By showing for the first time how a high fat diet and LCFAs affect hormone-induced lipolysis in fat cells, this study paves the way for further research on the role of various fatty acids on the metabolism of muscle and blood vessel cells, the researchers conclude.

———————————–
Article adapted by MD Only from original press release.
———————————–

Article: “Acute exposure to long-chain fatty acids impairs alpha2-adrenergic receptor-mediated antilipolysis in human adipose tissue,” by Jan Polak, Cedric Moro, David Bessiere, Jindra Hejnova, Marie A. Marques, Magda Bajzova, Max Lafontan, Francois Crampes, Michel Berlan, and Vladimir Stich

MEDIA CONTACT: Max Lafontan, Institut National de la Sante et de la Recherche Medicale (French National Institute of Health and Medical Research), Toulouse, France; e-mail: Max.Lafontan@toulouse.inserm.fr

Brisk Walk Helps You Stop Snacking

Researchers at the University of Exeter have found that a walk of just fifteen minutes can reduce chocolate cravings. The benefits of exercise in helping people manage dependencies on nicotine and other drugs have previously been recognised. Now, for the first time, newly-published research shows that the same may be true for food cravings.

Following three days of abstinence, 25 regular chocolate eaters were asked to either complete a 15-minute brisk walk or rest, in a random order. They then engaged in tasks that would normally induce chocolate cravings, including a mental challenge and opening a chocolate bar.

After exercise participants reported lower cravings than after rest. Cravings were not only reduced during the walk, but for at least ten minutes afterwards. The exercise also limited increases in cravings in response to the two tasks.

Professor Adrian Taylor comments: “Our ongoing work consistently shows that brief bouts of physical activity reduce cigarette cravings, but this is the first study to link exercise to reduced chocolate cravings. Neuroscientists have suggested common processes in the reward centres of the brain between drug and food addictions, and it may be that exercise effects brain chemicals that help to regulate mood and cravings. This could be good news for people who struggle to manage their cravings for sugary snacks and want to lose weight.”

Previous research has suggested that 97% of women and 68% of men experience food cravings. Craved foods tend to be calorie-dense, fatty or sugary foods, with chocolate being the most commonly reported. Chocolate has a number of biologically active constituents that temporarily enhance our mood with a result that eating it can become a habit, particularly when we are under stress and when it is readily available, and perhaps when we are least active.

Professor Taylor concludes: “While enjoying the occasional chocolate bar is fine, in time, regular eating may lead to stronger cravings during stress and when it is readily available. Recognising what causes us to eat high energy snacks, even if we have plans to not do so, can be helpful.”

“Short bouts of physical activity can help to regulate how energised and pleasant we feel, and with a sedentary lifestyle we may naturally turn to mood regulating behaviours such as eating chocolate. Accumulating 30 minutes of daily physical activity, with two 15 minute brisk walks, for example, not only provides general physical and mental health benefits but also may help to regulate our energy intake. This research furthers our understanding of the complex physical, psychological and emotional relationship we have with food.”

—————————-
Article adapted by MD Only from original press release.
—————————-

Contact: Sarah Hoyle
University of Exeter

Spices protect against the consequences of high blood sugar

Herbs and spices are rich in antioxidants, and a new University of Georgia study suggests they are also potent inhibitors of tissue damage and inflammation caused by high levels of blood sugar.

Researchers, whose results appear in the current issue of the Journal of Medicinal Food, tested extracts from 24 common herbs and spices. In addition to finding high levels of antioxidant-rich compounds known as phenols, they revealed a direct correlation between phenol content and the ability of the extracts to block the formation of compounds that contribute to damage caused by diabetes and aging.

“Because herbs and spices have a very low calorie content and are relatively inexpensive, they’re a great way to get a lot of antioxidant and anti-inflammatory power into your diet,” said study co-author James Hargrove, associate professor of foods and nutrition in the UGA College of Family and Consumer Sciences.

Hargrove explained that when blood sugar levels are high, a process known as protein glycation occurs in which the sugar bonds with proteins to eventually form what are known as advanced glycation end products, also known as AGE compounds. The acronym is fitting because these compounds activate the immune system, resulting in the inflammation and tissue damage associated with aging and diabetes.

The researchers found a strong and direct correlation between the phenol content of common herbs and spices and their ability to inhibit the formation of AGE compounds. Spices such as cloves and cinnamon had phenol levels that were 30 percent and 18 percent of dry weight, respectively, while herbs such as oregano and sage were eight and six percent phenol by dry weight, respectively. For comparison, blueberries – which are widely touted for their antioxidant capabilities – contain roughly five percent phenol by dry weight.

Study co-author Diane Hartle, associate professor in the UGA College of Pharmacy, said various phenols are absorbed differently by the body and have different mechanisms of action, so it’s likely that a variety of spices will provide maximum benefit.

“If you set up a good herb and spice cabinet and season your food liberally, you could double or even triple the medicinal value of your meal without increasing the caloric content,” she said.

She added that controlling blood sugar and the formation of AGE compounds can also decrease the risk of cardiovascular damage associated with diabetes and aging. She explained that high blood sugar accelerates heart disease partly because AGE compounds form in the blood and in the walls of blood vessels. The AGE compounds aggravate atherosclerosis, which produces cholesterol plaques.

The UGA researchers tested for the ability to block AGE compounds in a test tube, but animal studies conducted on the health benefits of spices lend support to their argument. Cinnamon and cinnamon extracts, for example, have been shown to lower blood sugar in mice. Interestingly, cinnamon lowers blood sugar by acting on several different levels, Hargrove said. It slows the emptying of the stomach to reduce sharp rises in blood sugar following meals and improves the effectiveness, or sensitivity, of insulin. It also enhances antioxidant defenses.

Hargrove said their findings suggest it’s likely that the herbs and spices they studied will provide similar benefits in animal tests. He points out that because humans have been consuming herbs and spices for thousands of years, they come without the risk of possible side effects that accompany medications.

“Culinary herbs and spices are all generally recognized as safe and have been time-tested in the diet,” he said. “Indeed, some of spices and herbals are now sold as food supplements because of their recognized health benefits.”

Study co-author Phillip Greenspan, associate professor in the College of Pharmacy, noted that most people don’t get their recommended five to nine servings of fruits and vegetables a day. Rather than seasoning their food with salt – which provides no beneficial phenols and has been linked to high blood pressure – he recommends that people use a variety of herbs and spices to help boost the nutritional quality of their meals.

“When you add herbs and spices to food, you definitely provide yourself with additional benefits besides taste,” Greenspan said.

—————————-
Article adapted by MD Only from original press release.
—————————-

Contact: Sam Fahmy
University of Georgia

Weight-loss more effective than insulin for type 2 diabetics

DALLAS — March 11, 2008 — Weight-loss and major lifestyle changes may be more effective than intensive insulin therapy for overweight patients with poorly controlled, insulin-resistant type 2 diabetes, according to a diabetes researcher at UT Southwestern Medical Center.

The National Heart, Lung, and Blood Institute of the National Institutes of Health recently halted part of an ongoing clinical trial on diabetes and heart disease after more than 250 people died while receiving intense treatment to drive their blood glucose levels below current clinical guidelines.

The evidence is compelling that when insulin levels are high, certain tissues are overloaded with fatty molecules, which leads to insulin resistance. And yet, the high blood glucose levels of many obese patients with insulin-resistant type 2 diabetes are being treated with increasing amounts of insulin in an attempt to overpower that resistance. While high doses of insulin may lower glucose levels, it will also increase the fatty molecules and may cause organ damage. 

In a commentary in the March 12 issue of The Journal of the American Medical Association, Dr. Roger Unger, professor of internal medicine, wrote about the recent findings of his own and other labs that link insulin resistance to excess accumulation of fatty molecules in liver and muscle.

Dr. Unger, who has investigated diabetes, obesity and insulin resistance for more than 50 years said intensive insulin therapy is contraindicated for obese patients with insulin-resistant type 2 diabetes because it increases the fatty acids that cause diabetes. Instead, the most rational therapy eliminates excess calories, thereby reducing the amount of insulin in the blood and the synthesis of the fatty acids stimulated by the high insulin. Giving more insulin simply increases body fat.  

“Evolution was unprepared for the change in the American diet to processed fast food and drive-through lanes,” he said. “There’s no way that our genes could evolve to gird themselves against the superabundance of very, very high-calorie foods that have flooded the U.S.”

Before the discovery of insulin, starvation was the only treatment for diabetes, said Dr. Unger, who is a member of the National Academy of Sciences.

“Today there are many treatment options, including bariatric surgery, if necessary, to lower the fat content in the body before you start giving insulin,” he said. “The fat is causing insulin resistance and killing the insulin-producing beta cells in the pancreas — that is what is causing type 2 diabetes.”

Giving more insulin simply channels the glucose into fat production. There is now a spectrum of therapies that improve diabetes by correcting the insulin resistance by reducing the body fat. Insulin treatment would be indicated only if all these fail.

Dr. Unger said insulin should be given to patients with insulin deficiency, but not if the insulin levels are already very high but ineffective. “Giving more insulin to an insulin-resistant patient is akin to raising the blood pressure of a patient with high blood pressure to overcome resistance to blood flow. Instead, you would try to reduce the resistance,” he said.

In the commentary, Dr. Unger said the increase in the number of patients with insulin-resistant type 2 diabetes can be traced to the epidemic of obesity that began in the U.S. after World War II, when food preparation was moved from the family kitchen to factories and companies that produce high-fat, calorie-dense foods, leading both men and women to consume substantially more calories on a daily basis. In addition, technological advancements such as televisions, computers and automobiles reduced the number of calories burned per day.

Type 2 diabetes occurs when the body is unable to make enough of the hormone insulin to compensate for insulin resistance. The condition affects between 18 million and 20 million people in the U.S.

Factors that increase the risk of type 2 diabetes include obesity, age and lack of exercise. Over a period of years, high blood sugar damages nerves and blood vessels, leading to complications such as heart disease, stroke, blindness and kidney disease. 

Dr. Unger’s research is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the Department of Veterans Affairs, and the Juvenile Diabetes Research Foundation.

—————————-
Article adapted by MD Only from original press release.
—————————-

Contact: Kristen Holland Shear
UT Southwestern Medical Center

A brisk walk daily is the easiest way to trim waistline

Research from Duke University Medical Center shows that even a modest amount of brisk walking weekly is enough to trim waistlines and cut the risk of metabolic syndrome (MetS), an increasingly frequent condition linked to obesity and a sedentary lifestyle.

It’s estimated that about a quarter of all U.S. adults have MetS, a cluster of risk factors associated with greater likelihood of developing heart disease, diabetes and stroke: large waist circumference, high blood pressure, high levels of triglycerides, low amounts of HDL, or “good” cholesterol, and high blood sugar. To be diagnosed with MetS, patients must have at least three of these five risk factors, and according to many studies, a growing number of people do.

But Johanna Johnson, a clinical researcher at Duke Medical Center and the lead author of a new study examining the impact of exercise on MetS, said a person can lower risk of MetS by walking just 30 minutes a day, six days per week. “That’s about 11 miles per week. And our study shows that you’ll benefit even if you don’t make any dietary changes.”

“The results of our study underscore what we have known for a long time,” said Duke cardiologist William Kraus. “Some exercise is better than none; more exercise is generally better than less, and no exercise can be disastrous.”

The study appears in the December 15 issue of the American Journal of Cardiology.

The results come from a multi-year, federally funded study called STRRIDE (Studies of a Targeted Risk Reduction Intervention through Defined Exercise) that examined the effects of varying amounts and intensity of exercise on 171 middle-aged, overweight men and women.

Before exercising regularly, 41 percent of the participants met the criteria for MetS. At the end of the 8-month exercise program, only 27 percent did.

“That’s a significant decline in prevalence,” said Johnson. “It’s also encouraging news for sedentary, middle-aged adults who want to improve their health. It means they don’t have to go out running four or five days a week; they can get significant health benefits by simply walking around the neighborhood after dinner every night.”

Still, some exercise regimens were better than others. Those who exercised the least, walking about 11 miles per week, gained significant benefit, while those who exercised the most, jogging about 17 miles per week, gained slightly more benefit in terms of lowered MetS scores.

One group puzzled the researchers, however. Those who did a short period of very vigorous exercise didn’t improve their MetS scores as much as those who performed less intense exercise a longer period.

Kraus said there may be more value in doing moderate intensity exercise every day rather than more intense activity just a few days a week.

In all three of the study’s exercise groups, waistlines got smaller over the 8-month period. In general, men who exercised saw greater improvement in their MetS risk factors than women. But Johnson points out that at baseline, the men generally had worse scores than women, “so they had more room to improve,” she said.

Over the course of the STRRIDE study, the inactive control group – those who didn’t change their diet or activity level at all – gained an average of about one pound and a half-inch around the waist. “That may not sound like much, but that’s just six months,” Kraus said. “Over a decade, that’s an additional 20 pounds and 10 inches at the beltline.”

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Michelle Gailiun
Duke University Medical Center

The study was funded by the National Institutes of Health.

Colleagues at Duke who contributed to the study include Cris Slentz, Gregory Samsa, Lori Bateman and Brian Duscha. Collaborating authors from East Carolina University include Joseph Houmard, Jennifer McCartney and Charles Tanner.

Overeating disrupts body clock causes weight gain

Our body’s 24-hour internal clock, or circadian clock, regulates the time we go to sleep, wake up and become hungry as well as the daily rhythms of many metabolic functions. The clock — an ancient molecular machine found in organisms large and small, simple and complex — properly aligns one’s physiology with one’s environment.Now, for the first time, a Northwestern University and Evanston Northwestern Healthcare (ENH) study has shown that overeating alters the core mechanism of the body clock, throwing off the timing of internal signals, including appetite control, critical for good health. Animals on a high-fat diet gained weight and suddenly exhibited a disruption in their circadian clocks, eating extra calories during the time they should have been asleep or at rest.

The study, which will be published in the Nov. 7 issue of the journal Cell Metabolism, also shows that changes in metabolic state associated with obesity and diabetes not only affects the circadian rhythms of behavior but also of physiology. Probing beyond the behavioral level, the researchers observed actual changes in genes that encode the clock in the brain and in peripheral tissues (such as fat), resulting in diminished expression of those genes.

These findings close an important loop in studies led by Joe Bass, M.D., assistant professor of medicine and neurobiology and physiology at Northwestern and head of the division of endocrinology and metabolism at ENH, of the relationship between the body clock and metabolism. Two years ago Bass and his colleagues reported in the journal Science that a faulty or misaligned body clock can wreak havoc on the body and its metabolism, increasing the propensity for obesity and diabetes.

Since then, knowing that genetic mutations rarely are the reason for a malfunctioning body clock, Bass has been wondering what could upset the operation of this internal timing device. What are the environmental factors or common influences that might affect the clock and in turn disrupt the sleep/wake cycle”

“Our study was simple — to determine if food itself can alter the clock,” said Bass, senior author of the paper. “The answer is yes, alterations in feeding affect timing. We found that as an animal on a high-fat diet gains weight it eats at the inappropriate time for its sleep/wake cycle — all of the excess calories are consumed when the animal should be resting. For a human, that would be like raiding the refrigerator in the middle of the night and binging on junk food.”

The clock-metabolism cycles feed on each other, creating a vicious loop, says Bass. Once weight gain starts, the clock is disrupted, and a disrupted clock exacerbates the original problem, affecting metabolism negatively and increasing the propensity for obesity and diabetes.

“Timing and metabolism evolved together and are almost a conjoined system,” said Bass. “If we perturb the delicate balance between the two, we see deleterious effects.”

The biological clock is central to behavior and tissue physiology. Clocks function in the brain as well as lung, liver, heart and skeletal muscles. They operate on a 24-hour, circadian (Latin for “about a day”) cycle that governs functions like sleeping and waking, rest and activity, fluid balance, body temperature, cardiac output, oxygen consumption and endocrine gland secretion.

In their study, Bass and his team studied mice with the same genetic backgrounds. After feeding them a regular diet for two weeks, they were split into two groups for the remaining six weeks, one kept on a regular diet and the other fed a high-fat diet. After two weeks, those on the high-fat diet showed a spontaneous shift in their normal pattern of activity/eating and resting/sleeping. They began to eat during their typical rest or sleep period (daylight for a mouse). The animals on a regular diet did not exhibit this behavior.

“It’s not just that the animals are eating more at regular meals,” said Bass. “What’s happened is that they actually shift their eating habits so that all excess food intake occurs during their normal rest period.”

In the study’s high-calorie, high-fat diet, 45 percent of calories was contributed by fat. For humans, a diet with no more than 30 percent of calories from fat is recommended.

The entire study was conducted in darkness so that the behavior of the animals simply reflected their internal clock; a normal animal has a very fixed daily period of just less than 24 hours. For animals on a high-fat diet, after two weeks on that diet the animals’ behavior changed: their daily period of sleep/wake was lengthened by a significant amount. This suggests, says Bass, that the central mechanism in the brain that controls the timing of the cycle of activity and rest is affected by a high-fat diet.

“Our findings have implications for human disease,” said Bass. “These basic advances in science can be applied to the studies of common disorders like obesity and diabetes. It is important to understand what happens when diet changes.”

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Wendy Leopold
Northwestern University

In addition to Bass, other authors of the paper, titled “High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice,” are Akira Kohsaka, of Northwestern (lead author); Aaron Laposky, research assistant professor at Northwestern’s Center for Sleep and Circadian Biology; Kathryn Moynihan Ramsey, Carmela Estrada and Corrine Joshu, of Northwestern; Yumiko Kobayashi, of Evanston Northwestern Healthcare; and Fred W. Turek, professor of neurobiology and physiology at Northwestern and director of the Center for Sleep and Circadian Biology.

Plant pigment in cherries helps lower sugar levels

Perhaps George Washington wouldn’t have chopped down his father’s cherry tree if he knew what chemists now know. They have identified a group of naturally occurring chemicals abundant in cherries that could help lower blood sugar levels in people with diabetes. In early laboratory studies using animal pancreatic cells, the chemicals, called anthocyanins, increased insulin production by 50 percent, according to a peer-reviewed study scheduled to appear in the Jan. 5 issue of the American Chemical Society’s Journal of Agricultural and Food Chemistry. ACS is the world’s largest scientific society.Anthocyanins are a class of plant pigments responsible for the color of many fruits, including cherries. They also are potent antioxidants, highly active chemicals that have been increasingly associated with a variety of health benefits, including protection against heart disease and cancer.

“It is possible that consumption of cherries and other fruits containing these compounds [anthocyanins] could have a significant impact on insulin levels in humans,” says study leader Muralee Nair, Ph.D., a natural products chemist at Michigan State University in East Lansing. “We’re excited with the laboratory results so far, but more studies are needed.” Michigan is the top cherry producing state in the nation.

Until human studies are done on cherry anthocyanins, those with diabetes should continue following their doctor’s treatment recommendations, including any medicine prescribed, and monitor their insulin carefully, the researcher says. The compounds show promise for both the prevention of type 2 (non-insulin-dependent) diabetes, the most common type, and for helping control glucose levels in those who already have diabetes, he adds.

While fresh cherries and fruits containing these anthocyanins are readily available, medicinal products may be the most efficient way to provide the beneficial compounds, according to Nair. It’s possible that anthocyanins eventually could be incorporated into new products, such as pills or specialty juices that people could take to help treat diabetes. Such disease-specific products may take several more years to develop, he notes.

Scientists in Nair’s laboratory have even developed a unique process, patented by the university, for removing sugar from fruit extracts that contain anthocyanins. This could lead to “sugar-free” medicinal products for people with diabetes.

The current study, partially funded by the U.S. Department of Agriculture, involved tart cherries (also known as sour cherries or pie cherries), a popular variety in the United States, and the Cornelian cherry, which is widely consumed in Europe. Nair and his associates, B. Jayaprakasam, Ph.D., L.K. Olson, Ph.D., and graduate student S. K. Vareed, tested several types of anthocyanins extracted from these cherries against mouse pancreatic-beta cells, which normally produce insulin, in the presence of high concentrations of glucose.

Insulin is the protein produced by the pancreas that helps regulate blood sugar (glucose) levels. Compared to cells that were not exposed to anthocyanins, exposed cells were associated with a 50 percent increase in insulin levels, the researchers say. The mechanism of action by which these anthocyanins boost insulin production is not known, Nair says.

Nair and his colleagues are currently feeding anthocyanins to a group of obese, diabetic mice to determine how the chemicals influence insulin levels in live subjects. Results of these tests are not yet available.

Although other fruits, including red grapes, strawberries and blueberries, also contain anthocyanins, cherries appear to be the most promising source of these compounds on the basis of serving size, according to the researcher. The compounds are found in both sweet and sour (tart) cherry varieties.

The potential benefits of cherries extend beyond diabetes. Previous studies by the researcher found that certain anthocyanins isolated from cherries have anti-inflammatory properties and may be useful in fighting arthritis. Nair’s colleagues have found that cherries also may help fight colon cancer.

But people with diabetes are encouraged to use caution when it comes to consuming maraschino cherries, the bright red candied version that adorns ice cream and cocktails, Nair points out. Many of the beneficial cherry pigments that were present in the fresh fruit have been removed during processing, replaced with food coloring, and extra sugar has been added.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 159,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: Michael Bernstein
American Chemical Society

Ginseng extract fights diabetes, lowers cholesterol and decreases weight

An extract from the ginseng berry shows real promise in treating diabetes and obesity, reports a research team from the University of Chicago’s Tang Center for Herbal Medicine Research. In the June issue of the journal Diabetes, they show that the extract completely normalized blood glucose levels, improved sensitivity to insulin, lowered cholesterol levels, and decreased weight by reducing appetite and increasing activity levels in mice bred to develop diabetes.For more than 2000 years, traditional Chinese medicine has used ginseng root to treat a variety of ailments. This study focused instead on substances found in the ginseng berry, which has very different concentrations of ginsenosides, the substances thought to be medically useful.

“Ginseng berry has a distinctive chemical profile and has not previously been used for therapy,” said Chun-Su Yuan, M.D., Ph.D., assistant professor of anesthesia and critical care at the University of Chicago and director of the study. “We were stunned by how different the berry is from the root and by how effective it is in correcting the multiple metabolic abnormalities associated with diabetes.”

Yuan’s team, which included researchers from the Tang Center, anesthesia, clinical pharmacology and medicine, studied the effects of the extract, made from the pulp of the berry. They also studied one particular substance known as ginsenoside Re, which is concentrated in ginseng berries but quite scarce in the root.

They tested the extract by injecting it once a day into mice with a gene defect that causes weight gain and type 2 diabetes. They found that —

• Daily injections of 150 mg/kg of the ginseng berry extract restored normal blood-sugar levels in diabetic mice. Blood-glusoce levels fell from 222 mg/dl (quite high for a mouse) to 137 mg/dl (normal) within 12 days. Treated mice also had better scores on a glucose tolerance test, which measures how quickly the mice could remove excess glucose from the blood.
• The extract caused diabetic mice, which were also obese, to lose more than 10 percent of their body weight in 12 days. Untreated mice gained five percent of their weight in 12 days. The treated mice ate 15 percent less and were 35 percent more active than untreated mice. Once the injections stopped, weight gain gradually resumed.
• The extract improved insulin secretion and insulin sensitivity, both of which were abnormal in mice with diabetes.
• Treated diabetic mice had 30 percent lower cholesterol levels than untreated diabetic mice (117mg/dl versus 169mg/dl).

The extract had no detectable effect on normal mice.

Tests using a ginsenoside Re alone found that it had all of the anti-diabetic but none of the obesity-fighting activities of the extract.

“This novel compound could serve as the basis for a whole new class of anti-diabetic medications,” said Yuan, who is also working to isolate other substances from the extract that contributed to the weight loss.

There is a pressing need for new and more effective drugs for both diabetes and obesity. Diabetes is the seventh leading killer in the U.S. Type 2 diabetes affects almost six percent of the U.S. population and 18.4 percent of those over 65. The cost of the disease is estimated at $105 billion each year.

The U.S. Surgeon General estimates that 61 percent of adults are overweight or obese. Obesity — wieghing more than 20 percent over your maximum recommended body weight — contributes to an estimated 300,000 deaths each year. The economic cost of obesity in the U.S. was about $117 billion in 2000. The rising rate of obesity also contributes to the growing prevalence of type 2 diabetes.

“Since this berry contains agents that are effective against both obesity and diabetes, the ginseng fruit has enormous promise as a source of new drugs,” said Yuan, who has worked with the University to apply for a patent on the development of ginsenoside Re as a diabetes medication.

“The next step is to isolate the other substances in the extract, find out whether they also effect glucose regulation or weight gain, learn how they work and determine the safe and effective dose.”

—————————-
Article adapted by MD Only Weblog from original press release.
—————————-

Contact: John Easton
University of Chicago Medical Center

Additional authors of the study were Anoja Attele, Yun-Ping Zhou, Jing-Tian Xie, Ji An Wu, Liu Zhang, Lucy Dey, William Pugh and Paul Rue of the University of Chicago and Kenneth Polonsky, now at Washington University in St. Louis. The research was funded by the Tang Family Foundation and the National Institutes of Health.