A new study finds that restricted nutrient availability prevents muscle stem cells from growing into mature muscle cells. The research, published by Cell Press in the May issue of the journal Developmental Cell, provides exciting new information about how developing muscle cells sense and respond to nutrient levels. The study adds a new twist to ongoing research into the effects of caloric restriction on physiology and aging and may lead to new therapeutic avenues for muscle wasting.

Although it is certainly rational to expect that access to nutrients, such as the simple sugar glucose, has a profound impact on the development of human cells, the cellular strategies for responding to fluctuations in nutrient availability are not well understood. Drs. Vittorio Sartorelli and Marcella Fulco from the National Institutes of Health investigated how the availability of glucose affects the ability of muscle stem cells, called myoblasts, to develop (or “differentiate”) into mature skeletal muscle fibers.

The researchers found that glucose restriction (GR) impaired differentiation of skeletal myoblasts and activated AMP-activated protein kinase (AMPK). These results define a pathway in which activation of AMPK in response to low glucose levels stimulates expression of the NAD+ biosynthetic enzyme Nampt. NAD+ is a known cofactor of SIRT1, which plays an important role in numerous physiological processes, including differentiation of skeletal muscle cells, and has been implicated in regulation of lifespan and aging. Importantly, inhibition of AMPK, Nampt or SIRT1 resulted in skeletal muscle cells that were oblivious to a nutrient poor environment and were able to differentiate under conditions that otherwise would not be suitable.

These results demonstrate that a defined pathway actively controls muscle differentiation in response to low nutrients. “We speculate that, functioning as a cellular checkpoint, the AMPK-Nampt-SIRT1 pathway may be activated by reduced nutrient availability to prevent cells from undertaking energy demanding processes – such as cell differentiation – during calorie-unfavorable conditions. On the other hand, once nutrients become available, the pathway is inactivated to allow resumption of physiological development,” offers Dr. Sartorelli.

The study has important implications that extend beyond muscle development. This mechanism also operates in adult tissues and thus would be part of the response to a dietary regimen that restricts caloric intake. Further, the researchers found that glucose restriction or treatment of skeletal muscle cells with metformin, a drug used to treat type II diabetes, had similar outcomes and resulted in the activation of SIRT1. “It is therefore possible that the well-known benefits that diabetics derive from lowering the calorie intake in their diet may be attributable to activation of the AMPK-Nampt-SIRT1 axis” comments Dr. Sartorelli. It is also attractive to speculate that AMPK and SIRT1 may prove to be rational targets for counteracting the devastating effects of muscle wasting.

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The researchers include Marcella Fulco, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD; Yana Cen, Weill Medical College of Cornell University, New York, NY; Po Zhao, Children’s National Medical Center, Washington, DC; Eric P. Hoffman, Children’s National Medical Center, Washington, DC; Michael W. McBurney, Ottawa Health Research Center Institute, Ottawa, Canada; Anthony A. Sauve, Weill Medical College of Cornell University, New York, NY; and Vittorio Sartorelli, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD.

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Being able to enjoy your favorite foods, feel full after meals — and still lose weight — sounds like having your cake and eating it too.

But “feeling full on fewer calories” is exactly what is promised by a new approach to eating based on research conducted by Dr. Barbara Rolls, who holds Penn State’s Guthrie Chair of Nutrition in the College of Health and Human Development.

The eating plan is detailed in a new book, “Volumetrics: Feel Full on Fewer Calories,” to be published in January by HarperCollins. The authors are Rolls and nutrition writer Robert A. Barnett.

The basic strategy of “Volumetrics” — eat a satisfying volume of food while controlling calories and meeting nutrient requirements — is based on a series of studies conducted by Rolls in Penn State’s Laboratory for the Study of Human Ingestive Behavior over the last seven years.

These studies show that eating your usual amount but selecting low-energy density meals, which have fewer calories per ounce and contain lots of fruits and vegetables, offers a way to cut back on calories and still leave the table feeling full and satisfied.

“When we first started these studies, we thought that fat played an important role in satiety,” Rolls says. “We found that, when you keep the calories and volume of food that a person eats fairly constant, you don’t see any special effects for fat in terms of reducing hunger.”

The Rolls research team also investigated the effects of drinking water before or during meals. The results showed that the energy density of food mattered most in producing satiety, the feeling of leaving the table well satisfied.

Rolls explains that her group’s research has shown that feeling full depends on eating a satisfying amount of food. Tiny portions just don’t do it. The energy density of food, or the ratio of calories to the weight of food, is what matters most in order to feel full while controlling calories. Foods with a high energy density have lots of calories in a small serving and are typically lower in water content. For example, a 100-calorie serving of raisins, a high-energy density food, is only one-quarter cup. A 100-calorie serving of grapes, a food low in energy density and high in water content, is one and two thirds cups.

In one Penn State study, women who had a low energy density soup as a first course, ate fewer calories overall during lunch. However, soup is not the only water-rich food that can help decrease calorie intake, says Rolls. She says her group’s research has shown that by consuming other water-rich foods, too, dieters don’t have to limit portion size to less than what they normally consume.

Following your usual eating habits but modifying some favorite recipes to reduce the energy density is a sensible way of applying these research findings in a home kitchen, Rolls says.

For example you could reduce the energy density of chili by adding leaner meat, celery, extra tomatoes and mushrooms to increase bulk but not calorie content. Pasta salad bulked up with zucchini, carrots and other veggies, which have a high water content, can provide a portion double the size for the same calories as a pasta salad made with few veggies. Sprouts, lettuce and tomato can round out the satisfaction that a sandwich provides without increasing calories.

“People on diets often substitute pretzels for high-fat, high-calorie snacks. But pretzels have a low-water content and don’t fill you up, so you eat more of them. A snack with higher water and fiber content, for example, an apple, would be a better choice,” says the Penn State researcher.

Rolls’ new book provides more information about the energy density of specific foods along with menus, recipes, and tips for modifying favorite dishes. A Food Guide contains a list of more than 600 foods divided into four categories to help you select a satisfying lower-calorie diet. A menu planning section not only offers 50 recipes but also includes illustrated, step-by-step demonstrations on how to modify favorite dishes.

A section on the Active Life offers advice on becoming more physically active to help you burn more calories. The chapter on the Satiety Lifestyle shows you how much you eat depends on environmental factors from the size of the package you buy at the supermarket to whether you’re watching TV while you eat.

Rolls’ research shows that your body’s natural satiety sensors probably won’t even notice if you reduce the amount of calories and fat in meals by adding more water and fiber — and you can eat larger portions for the same calories. Her new book, “Volumetrics,” shows you how.

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Article adapted by MD Sports from original press release.
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Contact: Barbara Hale
Penn State

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Research

It’s fewer calories not Carbs or fluid loss responsible for weight loss.

PHILADELPHIA —  A new three-week in-hospital study of 10 volunteers found that during the two-week period on a strictly controlled very-low carbohydrate diet, participants lost an average of 3.6 pounds, voluntarily reduced their calorie intake from 3,111 calories per day to 2,164 calories per day, and did not eat more of the readily available fat and protein to make up for the lost carbohydrate calories.The study, “Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes,” compared a very low-carbohydrate diet with a regular diet. It is published in the March 15, 2005, issue of Annals of Internal Medicine and is the subject of a video news release.

During the first study week, participants, who were obese and had mild type 2 diabetes mellitus, ate a regular diet in which they could eat anything and as much as they wanted. They ate about 3,000 calories and 300 grams of carbohydrates per day and remained at entry weight.

In the following two weeks, when restricted to 20 grams of carbohydrates per day, as specified in the Atkins induction diet, and despite readily available protein and fat foods, the participants voluntarily ate about 1,000 fewer calories per day, a calorie intake considered appropriate to their height.

Participants’ blood sugar improved on the low-carb diet, with better insulin sensitivity and lower blood triglycerides and cholesterol levels.

“We proved that people lose weight on the Atkins diet because they eat less (consume fewer calories), not because they get bored with the diet or lose body water or because the carbohydrate calories are treated differently by the body than fat or protein calories,” said Guenther Boden, MD, a Laura H. Carnell Professor of Medicine and chief of the division of endocrinology/diabetes/metabolism at Temple University School of Medicine.

“All the weight loss was in fat,” said Boden, the lead study author. “We weighed and measured every calorie that participants ate and every calorie they spent. We knew what went in and what went out.”

“On the very low-fat diet, participants spontaneously reduced their calories by about 1,000 per day. One gram of fat equals 9 calories, so, doing the math, you can determine how much fat will be lost by cutting 1,000 calories.”

Boden also believes that the carbohydrates actually stimulated the patients’ big appetites during the regular-diet week.

“Participants went from an excessive caloric intake to a normal caloric intake for their height and weight when we reduced their carbohydrates. This indicates to me that it was the carbohydrates that stimulated the excessive appetite,” Boden said.

Throughout the three-week study, researchers weighed all food, monitored exercise, measured participants’ calorie energy intake, expenditure and body water composition, and tested blood sugar, cholesterol, and several hormone levels believed to be involved in appetite regulation.

“You don’t have to cut carbs as drastically as participants did,” said Boden. “If you cut carbs modestly, you cut calories, and you’ll lose weight.”

“The message is: Calories count,” Boden said. “If you want to lose weight, you have to decrease your food intake or increase your physical activity. It helps to know that carbohydrates make it more difficult to reduce food intake. So cutting the carbohydrates, at least to some extent, will help keep down the caloric intake. With fewer carbohydrates, you’re going to eat fewer total calories a day.”

George A. Bray, MD, Chief, Division of Clinical Obesity and Metabolism at the Pennington Biomedical Research Center in Baton Rouge, La., and a well-known researcher in obesity and diabetes, wrote an accompanying editorial, “Is There Something Special about Low-Carbohydrate Diets?”

Bray notes that the study is small but calls it “a nicely done, short-term metabolic ward study.” He says that using “many different diets with different approaches to food restriction for individual patients at different times in their efforts to lose weight may be the most effective way a clinician can use the available diets. … (I) am not yet convinced that one diet has any more value than another — they all have value.”

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Article adapted by MD Sports from original press release.
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Contact: Susan Anderson
American College of Physicians

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Negative Energy Balance

By Sandco Staff

University Park, Pa. - Female athletes often lose their menstrual cycle when training strenuously, but researchers have long speculated on whether this infertility was due to low body fat, low weight or exercise itself. Now, researchers have shown that the cause of athletic amenorrhea is more likely a negative energy balance caused by increasing exercise without increasing food intake.

“A growing proportion of women are susceptible to losing their menstrual cycle when exercising strenuously,” says Dr. Nancy I. Williams, assistant professor of kineseology and physiology at Penn State. “If women go six to 12 months without having a menstrual cycle, they could show bone loss. Bone densities in some long distance runners who have gone for a prolonged time period without having normal menstrual cycles can be very low.”

In studies done with monkeys, which show menstrual cyclicity much like women, researchers showed that low energy availability associated with strenuous exercise training plays an important role in causing exercise-induced amenorrhea. These researchers, working at the University of Pittsburgh, published findings in the Journal of Clinical Endocrinology and Metabolism showing that exercise-induced amenorrhea was reversible in the monkeys by increasing food intake while the monkeys still exercised.

Williams worked with Judy L. Cameron, associate professor of psychiatry and cell biology and physiology at the University of Pittsburgh. Dana L. Helmreich and David B. Parfitt, then graduate students, and Anne Caston-Balderrama, at that time a post-doctoral fellow at the University of Pittsburgh, were also part of the research team. The researchers decided to look at an animal model to understand the causes of exercise-induced amenorrhea because it is difficult to closely control factors, such as eating habits and exercise, when studying humans. They chose cynomolgus monkeys because, like humans, they have a menstrual cycle of 28 days, ovulate in mid-cycle and show monthly periods of menses.

“It is difficult to obtain rigorous control in human studies, short of locking people up,” says Williams.

Previous cross-sectional studies and short-term studies in humans had shown a correlation between changes in energy availability and changes in the menstrual cycle, but those studies were not definitive.

There was also some indication that metabolic states experienced by strenuously exercising women were similar to those in chronically calorie restricted people. However, whether the increased energy utilization which occurs with exercise or some other effect of exercise caused exercise-induced reproductive dysfunction was unknown.

“The idea that exercise or something about exercise is harmful to females was not definitively ruled out,” says Williams. “That exercise itself is harmful would be a dangerous message to put out there. We needed to look at what it was about exercise that caused amenorrhea, what it was that suppresses ovulation. To do that, we needed a carefully controlled study.”

After the researchers monitored normal menstrual cycles in eight monkeys for a few months, they trained the monkeys to run on treadmills, slowly increasing their daily training schedule to about six miles per day. Throughout the training period the amount of food provided remained the standard amount for a normal 4.5 to 7.5 pound monkey, although the researchers note that some monkeys did not finish all of their food all of the time.

The researchers found that during the study “there were no significant changes in body weight or caloric intake over the course of training and the development of amenorrhea.” While body weight did not change, there were indications of an adaptation in energy expenditure. That is, the monkeys’ metabolic hormones also changed, with a 20 percent drop in circulating thyroid hormone, suggesting that the suppression of ovulation is more closely related to negative energy balance than to a decrease in body weight.

To seal the conclusion that a negative energy balance was the key to exercise-induced amenorrhea, the researchers took four of the previous eight monkeys and, while keeping them on the same exercise program, provided them with more food than they were used to. All the monkeys eventually resumed normal menstrual cycles. However, those monkeys who increased their food consumption most rapidly and consumed the most additional food, resumed ovulation within as little as 12 to 16 days while those who increased their caloric intake more slowly, took almost two months to resume ovulation.

Williams is now conducting studies on women who agree to exercise and eat according to a prescribed regimen for four to six months. She is concerned because recreational exercisers have the first signs of ovulatory suppression and may easily be thrust into amenorrhea if energy availability declines. Many women that exercise also restrict their calories, consciously or unconsciously.

“Our goal is to test whether practical guidelines can be developed regarding the optimal balance between calories of food taken in and calories expended through exercise in order to maintain ovulation and regular menstrual cycles,” says Williams. “This would then ensure that estrogen levels were also maintained at healthy levels. This is important because estrogen is a key hormone in the body for many physiological systems, influencing bone strength and cardiovascular health, not just reproduction.”

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Article adapted by MD Sports from original press release.
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Contact: A’ndrea Elyse Messer
Penn State

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Nitrogen Balance

By Sandco Staff