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

Menopause can make you fat

New research on the effects of the female sex hormone estrogen in the brain lend credence to what many women have suspected about the hormonal changes that accompany aging: Menopause can make you fat.Scientists long have sought to understand how changes in hormones during menopause could account for the increase in appetite and accompanying weight gain that often occurs among aging women.

In a series of animal experiments described today at the 234^th national meeting of the American Chemical Society, the world’s largest scientific society, researchers showed how estrogen receptors located in the hypothalamus serve as a master switch to control food intake, energy expenditure and body fat distribution. When these receptors are destroyed, the animals immediately begin to eat more food, burn less energy and pack on pounds.

This research seems to support a link between estrogen and regulation of obesity, especially the dangerous accumulation of abdominal fat linked to heart disease, diabetes, and cancer, says Deborah J. Clegg, Ph. D., assistant professor of psychiatry at the University of Cincinnati Academic Health Center, who is directing the studies.

The findings may also help scientists develop more targeted hormone replacement therapies, capable of stimulating estrogen receptors in one part of the brain or body while dampening it in the next, Clegg says.

Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.

To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.

Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.

When estrogen levels in the VMN dipped, the animals’ metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.

The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.

Clegg now plans to perform a similar experiment to deactivate ER-alpha in the arcuate nucleus region of the hypothalamus. This region contains two populations of neurons: one puts the brake on food intake and the other stimulates food intake. Clegg anticipates that a loss of estrogen in this region may create an increase in the animals’ appetites as well as their weight.

Clegg says her studies address an area that is sorely needed given the incidence and impact of gender differences in obesity and its complications.

“The accumulation of abdominal fat puts both men and women at a heightened risk of cardiovascular disease, diabetes, and insulin resistance,” she says. “Women are protected from these negative consequences as long as they carry their weight in their hips and saddlebags. But when they go through menopause and the body fat shifts to the abdomen, they have to start battling all of these medical complications.”

By identifying the critical brain regions that determine where body fat is distributed, Clegg says her findings may help scientists design hormone replacement therapies to better manage and manipulate estrogen levels.

“If we could target those critical regions and estrogen receptors associated with weight gain and energy expenditure, we could perhaps design therapies that help women sidestep many of the complications brought on by the onset of menopause,” she says.

—————————-
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.

—Deborah J. Clegg, Ph.D., is assistant professor of psychiatry at the University of Cincinnati Academic Health Center in Cincinnati, Ohio.

Memory Loss… Cognitive Decline and Dementia Linked to Diet

Research has shown convincing evidence that dietary patterns practiced during adulthood are important contributors to age-related cognitive decline and dementia risk. An article published in Annals of the New York Academy of Sciences highlights information on the benefits of diets high in fruit, vegetables, cereals and fish and low in saturated fats in reducing dementia risk.

Adults with diabetes are especially sensitive to the foods they eat with respect to cognitive function. Specifically, an adult with diabetes will experience a decline in memory function after a meal, especially if simple carbohydrate foods are consumed. While the precise physiological mechanisms underlying these dietary influences are not completely understood, the modulation of brain insulin levels likely contributes.

This deficit can be prevented through healthful food choices at meals. The findings suggest that weight maintenance reduces the risk of developing obesity-associated disorders, such as high blood pressure and high cholesterol, and is an important component of preserving cognitive health.

The work shows another benefit of maintaining healthful eating practices with aging – the same ones proposed by most diabetes and heart & stroke foundations. “This type of information should be able to empower the individual, knowing that he/she can be actively engaged in activities and lifestyles that should support cognitive health with aging,” says Carol Greenwood, author of the study.

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

Contact: Sean Wagner
http://www.blackwellpublishing.com

_________________________________________________________________
This study, entitled “Dietary Influences on Cognitive Function with Aging,” is published in volume 1114 of the Annals of the New York Academy of Sciences: Healthy Aging and Longevity.

To view the abstract for this article, please click here.

Does High Meat Intake Lead to Obesity?

Meat consumption appears to be a factor for obesity in women, according to a new study presented at the 54th Annual Meeting of the American College of Sports Medicine (ACSM) in New Orleans. Although the reasons are still unclear, high meat intake was associated with obesity in a preliminary study sample of more than 280 women.

More than half of the women classified as having high meat intake were obese, according to body fat percentage. Conversely, only 18.6 percent of women classified as having low meat intake were obese.

The study divided participants into groups classified by low, moderate, and high meat intake per 1,000 calories consumed a day. The low intake group consumed less than 1.9 three-ounce servings of meat per day, as opposed to more than 3.18 servings for the high intake group. Participants were nonsmoking, premenopausal women whose diet was monitored during a seven-day period.

Lead study author Garrett Hoyt says he can only speculate on the physiological causes behind his findings, but several factors may be to blame.

“It’s possible that eating more meat causes people to weigh more, or that people who weigh more eat more meat,” Hoyt said. “That sounds odd, but it’s possible that diets with lots of meat consumption, like the Atkins diet, have attracted people with higher body fat percentages.”

Hoyt points out that vegetarians and semi-vegetarians have been shown to be consistently leaner than meat-eaters. This may be because meat consumption increases insulin levels, which may lead to a hormonal response that leads to body growth.

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

The conclusions outlined in this news release are those of the researchers only, and should not be construed as an official statement of the American College of Sports Medicine.

Contact: Communications and Public Information
American College of Sports Medicine 

The American College of Sports Medicine is the largest sports medicine and exercise science organization in the world. More than 20,000 international, national, and regional members are dedicated to advancing and integrating scientific research to provide educational and practical applications of exercise science and sports medicine.

Brain hormone wires people to be obese or thin

Some brains may be wired to encourage fidgeting and other restless behaviors that consume calories and help control weight, according to new research published by The American Physiological Society.

The study found that the brains of rats bred to be lean are more sensitive to a chemical produced in the brain, orexin A, which stimulates appetite and spontaneous physical activity such as fidgeting and other unconscious movements. Compared to rats bred to be obese, the lean rats had a far greater expression of orexin receptors in the hypothalamus.

“The greater expression of orexin receptors suggests the lean rats’ brains were more sensitive to the orexin the brain produces,” said Catherine M. Kotz, the study’s senior researcher. “The results point to a biological basis for being a couch potato.”

This line of research suggests that frequent minor unconscious movements such as fidgeting and other behaviors associated with restlessness burn calories and help control weight, Kotz said. Further, it suggests a strategy to reduce weight gain and could lead to the development of a drug to stimulate minor activity.

The study “Elevated hypothalamic orexin signaling, sensitivity to orexin A and spontaneous physical activity in obesity resistant rats,” appears in the online edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology published by The American Physiological Society. The study was done by Jennifer A. Teske and Allen S. Levine of the University of Minnesota and the Minnesota Obesity Center, St. Paul; Michael Kuskowski, VA Medical Center, Minneapolis; James A. Levine, Mayo Clinic, Rochester, Minnesota; and Catherine M. Kotz, the VA Medical Center, University of Minnesota, and the Minnesota Obesity Center.

Study looks at obese versus lean rats

“Many people focus on diet, but it may be more feasible for some people to stand or move more throughout the day” as a way to control their weight, Kotz said. Contrary to common belief, metabolism rates don’t vary greatly from person to person and weight gain usually results from eating too much, burning too few calories, or both, she said.

The researchers drew their conclusions after performing a series of experiments with obesity-prone and obesity-resistant rats. The obesity-prone strain was developed for obesity research by breeding obese rats with other obese rats. The obesity-resistant rats were developed by breeding lean rats with lean rats, Kotz noted. The study also employed a control group of normal laboratory rats.

Each rat consumed the same number of calories each day. The researchers took baseline measurements of each rat’s activity using sensors to measure even minor movements, such as grooming and standing.

They found that the lean group moved significantly more during this baseline period than the obese group, Kotz said. This was true even though the rats were young and both groups weighed the same — eliminating the obesity itself as the cause of the decreased movement. After the baseline data gathering, the researchers moved to the experimental part of the study.

Lean rats have elevated expression of orexin receptors

“We knew from previous studies that orexin stimulated physical activity, and so we wanted to find out whether it enhances activity more in lean rats than in obese rats, Kotz explained. The researchers injected orexin into the lateral hypothalamus area of the brains of both groups and found that the lean rats became even more active, while the obese rats didn’t respond much at all. “Not only do the lean rats have a higher base activity rate but they respond more to orexin,” she said.

Orexin must bind to receptors in the brain to produce increased activity, so the researchers reasoned that the lean rats must have more orexin receptors. When they did a blind analysis of the brains of obese and lean rats of various ages, they found that the lean rats had double the gene expression level of orexin receptors compared to the obese rats, Kotz explained.

The greater gene expression of orexin receptors does not conclusively prove that there are more orexin receptors, but it is highly suggestive of that finding. Kotz and her fellow researchers are now looking to see if the lean rats have a greater number of orexin receptors in their brains.

Activity level important to weight control

Because the rats in this study ate the same amount of food, the researchers concluded that the weight gain of the obese rats comes more from expending too few calories than from consuming too many. Other studies have shown that disabling the orexin system of lean rats causes them to eat less and move less, which leads them to become obese, Kotz said. When the orexin system is working optimally, the increase in eating which orexin causes is believed to be offset by increased physical activity, she said.

It would be impossible to do a similar study of the brain in humans. But one of the researchers, James Levine, found in a previous study with humans that lean individuals move about two hours per day more than obese individuals. What does this mean for those who are overweight?

“If we can get obese individuals to a slightly higher level of activity, that would be very beneficial,” Kotz concluded.

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

Contact: Christine Guilfoy
American Physiological Society

The link between lack of sleep and obesity traced to brain cells

A possible link between lack of sleep (insomnia) and obesity has been traced to hypocretin/orexin cells in the hypothalamus region of the brain that are easily excited and sensitive to stress, Yale School of Medicine researchers report in the April 2005 issue of Cell Metabolism.

“If these neurons are over-activated by environmental or mental stress in daily situations, they may support sustained arousal, triggering sleeplessness, leading to overeating,” said lead author Tamas Horvath, associate professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences (Ob/Gyn) and Neurobiology at Yale School of Medicine. “The more stress you have, the lower the threshold becomes for exciting these hypocretin neurons.”

Horvath and co-author Xiao-Bing Gao, assistant professor in Ob/Gyn, studied hypocretin/orexin neurons in mice using electrophysiology and electron microscopy. They found a unique, previously un-described organization of inputs on hypocretin neurons in which excitatory nerve junctions outnumber inhibitory contacts by almost 10 fold. Stressors such as fasting further excite these neurons.

“This unique wiring and acute stress-induced plasticity of the hypocretin neurons correlates well with its involvement in the control of arousal and alertness, which are vital to survival,” said Horvath. “But it may also be an underlying cause of insomnia and associated metabolic disturbances, including obesity. In addition, insomnia is characteristic of perimenopause (early onset of menopause), which may lead to increased prevalence of obesity in postmenopausal women.”

Previous studies demonstrated the association between lack of sleep and obesity and suggested a good night’s sleep to help obesity. Horvath found that the neurological basis of the link between obesity and insomnia make them both independent and related products of the overactivated hypocretin system. Therefore, he said, “people with weight and sleep problems could benefit from cutting back on stressful aspects of their lives, rather than trying to specifically medicate either insomnia or obesity.”

Obesity and metabolic disorders are a major cause of death and illness in the United States, with one of the highest financial burdens on the health care system.

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

Contact: Karen N. Peart
Yale University

Citation: Cell Metabolism Vol. 1, Issue 4 (April 2005).

CLA found to successfully treat diabetes in mice

Fatty acids commonly found in dairy products have successfully treated diabetes in mice, according to a researcher at Penn State. The compounds, known as conjugated linoleic acids (CLA), have also shown promising results in human trials, signaling a new way of potentially treating the disease without synthetic drugs.

“The compounds are predominantly found in dairy products such as milk, cheese and meat, and are formed by bacteria in ruminants that take linoleic acids – fatty acids from plants – and convert them into conjugated linoleic acids, or CLA,” says Jack Vanden Heuvel, professor of molecular toxicology in Penn State’s College of Agricultural Sciences and co-director of Penn State’s Center of Excellence in Nutrigenomics.

Researchers first became interested in CLA when it was shown to inhibit a variety of cancers such as breast, skin and colon in mice, and further research showed effects on circulating cholesterol and inflammation. These effects are the same as the newest generation of synthetic drugs used to treat diabetes in humans.

These synthetic drugs act by triggering a set of nuclear receptors called PPAR. In addition to being targets for a variety of clinically effective drugs, PPARs belong to a large family of proteins, and their biological purpose is to sense fatty acids and fatty acid metabolites within the cell, says Vanden Heuvel.

When the synthetic drugs interact with these protein receptors, it turns the receptor “on,” making it an active form of the protein, which then interacts with DNA and regulates gene expression. This increases the enzymes that process fatty acids and also increases the tissues’ sensitivity to insulin.

“We wondered if CLA was using the same mechanism, in which case it could be used as an anti-diabetes drug,” Vanden Heuvel says.

To test the idea, he used CLA on mice prone to adult onset (Type-2) diabetes. Results indicated that the mice had an improvement in insulin action, and a decrease in circulating glucose. Also, the mechanism was indeed similar to that of the drugs.

“Anti-diabetes drugs act the same way. They mimic the natural activators of the receptors by getting into the cell and interacting with the PPARs to regulate glucose and fat metabolism,” says Vanden Heuvel.

Early human trials indicate that when administered for longer than 8 weeks, CLA improves the body’s misregulation of insulin and lowers the level of glucose in the blood in patients with adult onset, or Type-2 diabetes, the most common form of this disease.

However, Vanden Heuvel cautions that while having a diet that is high in dairy and meat products, and thereby CLA, might have a health benefit, one must also be aware of other lipids present in these products, such as trans fatty acids. Instead, he suggests that in addition to a well-balanced diet, it is advantageous to incorporate CLA as a dietary supplement, or to seek out new products that enrich foods such as butter, margarine and ice cream with CLA.

“Adult-onset diabetes is fast becoming an epidemic and is largely associated with poor diet and nutrition and other lifestyle issues,” Vanden Heuvel says. The reason for the increase in diabetes may have to do with the ratio of so-called “good” and “bad” fats, with the average American diet containing too much of the “bad” fats. CLA, whose effect is very similar to fish oil, a source of “good” fat, could prove beneficial against Type-2 diabetes.

“And compared to the synthetic drugs used to treated this disease, CLA does not cause weight gain and may in fact decrease overall body fat,” says Vanden Heuvel, who has been granted a patent on the new method of treating diabetes with CLA.

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

Contact: Amitabh Avasthi
Penn State

CLA reduces weight, blood sugar and leptin levels

Supplementing the diet with a certain fatty acid may lead to better weight control and disease management in diabetics, a new study suggests.Diabetics who added an essential fatty acid called conjugated linoleic acid (CLA) to their diets had lower body mass as well as lower blood sugar levels by the end of the eight-week study. Hyperglycemia, or high blood sugar, is a hallmark of diabetes.

Researchers also found that higher levels of this fatty acid in the bloodstream meant lower levels of leptin, a hormone thought to regulate fat levels. Scientists think that high leptin levels may play a role in obesity, one of the biggest risk factors for adult-onset diabetes.

“In previous work, we found that CLA delayed the onset of diabetes in rats,” said Martha Belury, the senior author of the study and an associate professor of human nutrition at Ohio State University. “In this study, we found that it also helped improve the management of adult-onset diabetes in humans.”

CLA is made up of various fatty acid isomers – compounds that share the same chemical formula but differ in chemical structure. Related isomers can have very different effects.

In the current study, the researchers found that one particular CLA isomer, t10c12-CLA, helped control both body weight and leptin levels. Nutritionists sometimes call this isomer the 10-12, isomer.

The research appears in the January issue of the Journal of Nutrition. Belury conducted the study while with the department of foods and nutrition at Purdue University. She is continuing the research at Ohio State.

The researchers asked 21 people with adult-onset diabetes to take either a supplement containing a mix of rumenic acid and 10-12 isomer or a safflower oil supplement as a control. The group was divided roughly in half. Rumenic acid is the predominant isomer in foods that contain CLA, while the 10-12 isomer is less abundant.

Participants were instructed to take their respective supplements every day for eight weeks.

“The amount of CLA, how long it’s taken and the type taken all impact the fatty acid’s ability to affect obesity in humans, and therefore help manage diabetes.”

While CLA supplements are available to consumers, Belury encourages diabetics to get their CLA from food sources – primarily beef, lamb and dairy products.

“Not only does it taste better, it’s also safer and more beneficial to get the nutrients from food,” she said. “Besides, we don’t yet know the long-term effects of taking CLA in supplement form.”

At the end of the trial, the researchers took blood samples from each participant to check CLA levels. By then, fasting blood glucose levels had decreased in nine of the 11 people taking the CLA supplement, but only in two of the 10 taking safflower supplements, meaning that CLA was helping to control certain symptoms of diabetes.

Fasting blood glucose levels decreased nearly five-fold in patients taking CLA, compared to patients taking the safflower oil.

The researchers also studied the impact each isomer had on changes in body weight and levels of the hormone leptin.

It was the 10-12 isomer, and not rumenic acid, that was linked to a reduction in body weight and leptin levels. While the average weight loss among patients taking CLA supplements was small (about 3.5 pounds), they had been asked to not change their normal caloric intake during the study. The group taking safflower supplements neither lost nor gained weight. Leptin levels decreased in the CLA group, and rose slightly in the safflower group.

“The effect of the 10-12 isomer on reducing body mass and leptin levels was key,” Belury said, adding that other researchers have shown the 10-12 isomer to be helpful in reducing body mass in animals.

“The amount of CLA, how long it’s taken and the type taken all impact the fatty acid’s ability to affect obesity in humans, and therefore help manage diabetes,” Belury said.

A 2002 study conducted by the Diabetes Prevention Program Research Group found that a modest reduction in body weight resulted in a 58 percent reduction in the incidence of diabetes in a group of people at high risk for developing the disease.

Belury conducted the study with Annie Mahon of the department of foods and nutrition at Purdue University and Sebastiano Banni of the department of experimental biology at the University of Cagliari, Italy.

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

Contact: Martha A. Belury
Ohio State University