Brain fatty acid levels linked to depression

A group of Israel researchers has discovered that rats with increased levels of the omega-6 fatty acid, arachidonic acid, show signs of depression.  There is also evidence that  a dietary deficiency in omega-3 fatty acids may be associated with depression.  The  ”phospholipid hypothesis” postulates decreased omega-3 fatty acid intake could be responsible for some types of depression.

The details of their findings appear in the Journal of Lipid Research  showing that omega-3 fatty acid concentration in the blood of depressed patients is lower than that in control patients.  Dr. Green in collaboration with Dr Gal Yadid of Bar-Ilan University, Ramat Gan used the Flinders Sensitive Line rats to investigate the link between omega-3 fatty acids and depression. They examined the brains of the depressed rats and compared them with brains from normal rats. Surprisingly, they found that the main difference between the two types of rats was in omega-6 fatty acid levels and not omega-3 fatty acid levels. Specifically, they discovered that brains from rats with depression had higher concentrations of arachidonic acid, a long-chain unsaturated metabolite of omega-6 fatty acid.

Arachidonic acid is found throughout the body and is essential for the proper functioning of almost every body organ, including the brain. It serves a wide variety of purposes, from being a purely structural element in phospholipids to being involved in signal transduction and being a substrate for a host of derivatives involved in second messenger function.

“The finding that in the depressive rats the omega-3 fatty acid levels were not decreased, but arachidonic acid was substantially increased as compared to controls is somewhat unexpected,” admits Dr. Green. “But the finding lends itself nicely to the theory that increased omega-3 fatty acid intake may shift the balance between the two fatty acid families in the brain, since it has been demonstrated in animal studies that increased omega-3 fatty acid intake may result in decreased brain arachidonic acid.”

Although far less attention has been paid to dietary requirements for omega-6 fatty acids, which can be found in most edible oils and meat, perhaps in the future depression may be controlled by increasing omega-3 fatty acid intake and decreasing omega-6 fatty acid intake.

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

Contact: Nicole Kresge
American Society for Biochemistry and Molecular Biology 
The American Society for Biochemistry and Molecular Biology (ASBMB) is a nonprofit scientific and educational organization with over 11,000 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions, and industry.

The manuscript for the Journal of Lipid Research paper can be downloaded from clicking Here

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

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

Arthritis sufferers get relief with Boswellia in 7 days

An enriched extract of the ‘Indian Frankincense’ herb Boswellia serrata has been proven to reduce the symptoms of osteoarthritis. Research published today in BioMed Central’s open access journal Arthritis Research & Therapy has shown that patients taking the herbal remedy showed significant improvement in as little as seven days.

Osteoarthritis is the most common form of arthritis; it commonly affects weight-bearing joints such as the knees and hips, along with the hands, wrists, feet and spine. The symptoms include pain, stiffness and limited movement. This randomised, double-blinded, placebo-controlled trial of 70 patients will be of great interest to sufferers, especially those who don’t get adequate relief from existing treatments.

The study was led by Siba Raychaudhuri, a faculty member of the University of California, Davis, in the United States. According to Raychaudhuri, “The high incidence of adverse affects associated with currently available medications has created great interest in the search for an effective and safe alternative treatment”. The extract the authors used was enriched with 30% AKBA (3-O-acetyl-11-keto-beta-boswellic acid), which is thought to be the most active ingredient in the plant. Raychaudhuri said, “AKBA has anti-inflammatory properties, and we have shown that B. serrata enriched with AKBA can be an effective treatment for osteoarthritis of the knee”. This is a proprietary product developed by Laila Nutraceuticals.

B. serrata has been used for thousands of years in the Indian system of traditional medicine known as ‘Ayurveda’. This study is the first to prove that an enriched extract of the plant can be used as a successful treatment.

The same authors have previously tested the safety of their remedy in animal experiments. They say that, “In this study, the compound was shown to have no major adverse effects in our osteoarthritis patients. It is safe for human consumption and even for long-term use”.

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

Contact: Graeme Baldwin
BioMed Central 

 

References

1. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin(R) for treatment of osteoarthritis of the knee Krishanu Sengupta, Krishnaraju V Alluri, Andey Rama Sathis, Simanchala Mishra, Trimurtulu Golakoti, Kadainti VS Sarma, Dipak Dey and Siba P Raychaudhuri Arthritis Research & Therapy (in press)

2. Arthritis Research & Therapy is an international, peer-reviewed online and print journal, publishing original research, reviews, commentaries and reports. Studies relate to the rationale and treatment of arthritis, autoimmune disease and diseases of bone and cartilage. The journal is edited by Prof Peter E Lipsky (USA) and Prof Sir Ravinder N Maini (UK) and has an Impact Factor of 4.04.

3. BioMed Central (http://www.biomedcentral.com/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.

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

Early diet modification may prevent type 1 diabetes in children

Within the next 10 years the EU-funded Diabetes Prevention study, part of an international study called TRIGR (Trial to Reduce IDDM in the Genetically at Risk), coordinated at the University of Helsinki, Finland, will generate a definite answer to the question whether early nutritional modification may prevent type 1 diabetes later in childhood.

Type 1 diabetes is a growing health problem among European children. European data indicate that the disease incidence has increased five-six-fold among children under the age of 15 years after World War II, and there are no signs that the increase in incidence is levelling off. The most conspicuous increase has been seen among children under the age of 5 years.

The TRIGR study is the first study ever aimed at primary prevention of type 1 diabetes. The study is designed to answer to the question whether excluding cow’s milk protein from the infant’s diet decreases the risk of future diabetes. All subjects are followed for 10 years to get information on whether the dietary recommendations for infants at increased genetic risk of type 1 diabetes should be revised.

Starting in May 2002, 76 study centres from 15 countries (Australia, Canada, the Czech Republic, Estonia, Finland, Germany, Hungary, Italy, Luxembourg, the Netherlands, Poland, Spain, Sweden, Switzerland and USA) have been recruiting families for the study. To be eligible the newborn infant has to have at least one family member (mother, father and/or sib) affected by type 1 diabetes and carry a HLA genotype conferring increased risk for type 1 diabetes. The initial recruitment target of 2032 eligible infants was reached at the be-ginning of September 2006, but the Study Group has decided to continue recruitment till the end of December 2006 (when the EU contribution will finish) to make the study even more powerful statistically.

A majority of the study participants (52%) have been recruited in Europe. The International Coordinating Cen-tre (ICC) is located at the University of Helsinki, Helsinki, Finland and the Data Management Unit (DMU) at the University of South Florida, Tampa, Florida, USA. The trial has logistically been a true challenge for both the ICC and DMU. DMU has been successful in establishing a secure, real-time, web-based, interactive data management system that works extremely well. This system can be directly applied to future international mul-ticentre studies.

The TRIGR study is generating a wealth of information on breast-feeding practices, infant nutrition and growth in young children in various countries. At 2 weeks of age almost all the participating infants were breast-fed. Exclusive breast-feeding continued longer in Europe than in North America. More than one third of the infants (35 %) received other foods in addition to breast milk and/or infant formulas at the age of 4 months, while WHO recommends that supplementary food should be introduced at the earliest by the age of 6 months. In Europe the first foods to be introduced are typically vegetables and fruits, whereas gluten-free cereals are most commonly introduced in North America.

Newborn infants in Northern Europe (NE) had a higher birth weight but a shorter birth length than infants in Central and Southern Europe (CSE). The NE children remained heavier than those from CSE at least up to the age of 18 months. The NE children were also taller than the CSE children starting already from the age of 3 months up to the age of 18 months. Accelerated growth in infancy has been identified as a risk factor for type 1 diabetes later in childhood. Accordingly the observed growth pattern may contribute to the higher incidence of type 1 diabetes in NE compared to CSE.

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

Contact: Hans K. Åkerblom
University of Helsinki

More information:
Study websites: http://www.trigr.org

Soft drinks linked to development of diabetes in children

Researchers have found new evidence that soft drinks sweetened with high-fructose corn syrup (HFCS) may contribute to the development of diabetes, particularly in children. In a laboratory study of commonly consumed carbonated beverages, the scientists found that drinks containing the syrup had high levels of reactive compounds that have been shown by others to have the potential to trigger cell and tissue damage that could cause the disease, which is at epidemic levels. HFCS is a sweetener found in many foods and beverages, including non-diet soda pop, baked goods, and condiments. It is has become the sweetener of choice for many food manufacturers because it is considered more economical, sweeter and more easy to blend into beverages than table sugar. Some researchers have suggested that high-fructose corn syrup may contribute to an increased risk of diabetes as well as obesity, a claim which the food industry disputes. Until now, little laboratory evidence has been available on the topic.

In the current study, Chi-Tang Ho, Ph.D., conducted chemical tests among 11 different carbonated soft drinks containing HFCS. He found ‘astonishingly high’ levels of reactive carbonyls in those beverages. These undesirable and highly-reactive compounds associated with “unbound” fructose and glucose molecules are believed to cause tissue damage, says Ho, a professor of food science at Rutgers University in New Brunswick, N.J. By contrast, reactive carbonyls are not present in table sugar, whose fructose and glucose components are “bound” and chemically stable, the researcher notes.

Reactive carbonyls also are elevated in the blood of individuals with diabetes and linked to the complications of that disease. Based on the study data, Ho estimates that a single can of soda contains about five times the concentration of reactive carbonyls than the concentration found in the blood of an adult person with diabetes.

Ho and his associates also found that adding tea components to drinks containing HFCS may help lower the levels of reactive carbonyls. The scientists found that adding epigallocatechin gallate (EGCG), a compound in tea, significantly reduced the levels of reactive carbonyl species in a dose-dependent manner when added to the carbonated soft drinks studied. In some cases, the levels of reactive carbonyls were reduced by half, the researchers say.

“People consume too much high-fructose corn syrup in this country,” says Ho. “It’s in way too many food and drink products and there’s growing evidence that it’s bad for you.” The tea-derived supplement provides a promising way to counter its potentially toxic effects, especially in children who consume a lot of carbonated beverages, he says.

But eliminating or reducing consumption of HFCS is preferable, the researchers note. They are currently exploring the chemical mechanisms by which tea appears to neutralize the reactivity of the syrup.

Ho’s group is also probing the mechanisms by which carbonation increases the amount of reactive carbonyls formed in sodas containing HFCS. They note that non-carbonated fruit juices containing HFCS have one-third the amount of reactive carbonyl species found in carbonated sodas with HFCS, while non-carbonated tea beverages containing high-fructose corn syrup, which already contain EGCG, have only about one-sixth the levels of carbonyls found in regular soda.

In the future, food and drink manufacturers could reduce concerns about HFCS by adding more EGCG, using less HFCS, or replacing the syrup with alternatives such as regular table sugar, Ho and his associates say. Funding for this study was provided by the Center for Advanced Food Technology of Rutgers University. Other researchers involved in the study include Chih-Yu Lo, Ph.D.; Shiming Li, Ph.D.; Di Tan, Ph.D.; and Yu Wang, a doctoral student.

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

Contact: Charmayne Marsh
American Chemical Society

The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

 

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