If the current financial climate has taught us anything, it’s that a system where over-borrowing goes unchecked eventually ends in disaster.  It turns out this rule applies as much to our bodies as it does to economics.  Instead of cash, our body deals in energy borrowed from muscle and given to the brain.

Unlike freewheeling financial markets, the lending process in the body is under strict regulation to ensure that more isn’t lent than can be afforded.  New research by scientists at the Salk Institute for Biological Studies reveals just how this process is implemented.

“We have all seen the sub-prime mortgage crisis,” says Marc Montminy, M.D., Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology who led the current study.  “If you take out a loan, sooner or later you’ve got to pay your debt, and the same is true in fasting metabolism.”

The Salk researchers’ findings, which are published ahead of print in the Oct. 5 edition of the journal Nature, may pave the way for novel therapies for sufferers of metabolic diseases in whom such regulation can spiral out of control.

Most tissues in our bodies respond to fasting by switching from their usual high-octane energy source—glucose—to burning a low-octane, cheaper alternative-fat.  For our brains, however, only the high-performance fuel will do.  If no food-derived glucose is available, the body must manufacture its own supply to maintain the brain in the manner to which it is accustomed.  It does so by taking energy from muscle in the form of protein and converting it to glucose in the liver, a process known as gluconeogenesis.  The sugar is then shipped via the bloodstream to the brain to keep it running smoothly.

Gluconeogenesis needs to be turned on rapidly in response to fasting, but shutting it off again is just as crucial.  “You don’t want gluconeogenesis to be prolonged,” says postdoctoral researcher and co-first author Yi Liu, Ph.D. “Because it uses muscle as a protein source, it will eventually lead to muscle wastage.”  Adds Montminy, “The question has always been how is the production of glucose turned on, and how is shut off again?”

Previous work by the Montminy lab and others has shown that two key proteins, CRTC2 and FOXO1, are needed to turn on glucose-making genes during fasting.  CRTC2 is activated by glucagon, a hormone whose levels go up when we stop eating.  FOXO1, on the other hand, is activated when levels of the food-stimulated hormone insulin drop below a certain threshold.  CRTC2’s and FOXO1’s activity needs to be tightly regulated, since producing too much glucose would result in over-borrowing of energy from muscle tissue.

To uncover the mechanism that ensures that this doesn’t happen, the Salk researchers created mice containing the gene for luciferase, a light-emitting enzyme usually found in fireflies, engineered in such a way that it was only turned on when CRTC2 was active.  Using imaging equipment, they could then detect CRTC2 activity in the livers of live mice simply by measuring how much they glowed.

When the mice were fasted, CRTC2 was rapidly activated, and the livers lit up, but to the scientists’ surprise, after six hours the light went out.  Experimentally decreasing the levels of CRTC2 or FOXO1 confirmed there was a two-stage fasting-response.  Lowering CRTC2 reduced gluconeogenesis only early on, while less FOXO1 only affected late glucose production.  As in a relay race, during fasting the baton for glucose production appeared to be passed from CRTC2 in stage one to FOXO1 in stage two.

The crucial switch from CRTC2 to FOXO1 comes in the form of SIRT1, a nutrient sensor that accumulates in the late fasting stage.  Yi discovered that SIRT1 has opposite effects on CRTC2 and FOXO1: it sends the former to the recycling bin, while it activates the latter, and thus the baton is safely transferred from CRTC2 to the FOXO1.

Why does the body want to change between these two regulators of glucose production?  Again, it comes down to body economics.  CRTC2 acts as a rapid response unit to quickly produce high levels of glucose when it detects glucagon.  Switching to FOXO1 later on slows down this production to more sustainable levels, while at the same time helping to produce ketone bodies, an alternative fuel the brain can use that does not require taking protein from muscle.  “It is just like paying your loan back,” says Montminy.  “Later on you produce blood sugar at a different rate than you did at the beginning.”

Knowledge of how this nutrient switch is working may help design new drugs to regulate sugar levels in diabetes patients.  In, particular, chemical activators of the SIRT1 switch may be key.  “This way we could provide control for patients with insulin resistance,” says Montminy, “as typically their blood sugars are elevated after overnight fasting because the switches that regulate the glucose-producing enzymes are too active.”  Perhaps, then, a pharmacological rescue package for patients whose lending systems have been left unregulated may be on the horizon.

America does a mediocre job caring for its sickest people.  The nation, says a new report, gets a C.

Palliative care programs make patients facing serious and chronic illness more comfortable by alleviating their pain and symptoms and counseling patients and their families.

Only Vermont, Montana and New Hampshire earned an A, according to America’s Care of Serious Illness: A State-by-State Report Card on Access to Palliative Care in Our Nation’s Hospitals, a report based on a study in the October 2008 issue of the Journal of Palliative Medicine.  Three states – Oklahoma, Alabama and Mississippi – got an F.

“The good news is that hospitals nationwide have implemented palliative care programs quickly over the last six years,” said R. Sean Morrison, MD, director of the non-profit National Palliative Care Research Center and senior author of the study.  “The bad news is that if you live in the South or you have to rely on public or small community hospitals, you’re in trouble.”

Ninety million Americans are living with serious illnesses such as cancer, heart disease, diabetes, Parkinson’s, stroke and Alzheimer’s.  As the baby boomers age, this number will more than double over the next 25 years.

“Americans are living longer – but with serious illnesses,” said Dr. Diane E. Meier, director of the Center to Advance Palliative Care and co-author of the study.  “Without palliative care, people with serious illnesses like cancer often suffer unnecessarily from severe fatigue, pain, shortness of breath, nausea and other symptoms from their disease and treatments.”

The study suggests that in states with more palliative care programs, patients are less likely to die in the hospital; don’t have to go to the intensive care unit as much in the last six months of life; and spend fewer days in intensive care or the coronary unit in the last six months.

That also saves hospitals money, which could help lower health care costs.

When dining at Chinese Buffets, overweight individuals serve themselves and eat differently than normal weight individuals.  This may lead them to overeat, according to a recent study by Cornell University’s Food and Brand Lab.  Compared to normal weight diners, overweight individuals sat 16 feet closer to the buffet, faced the food, used larger plates, ate with forks instead of chopsticks, and served themselves immediately instead of browsing the buffet.

“What’s crazy is that these people are generally unaware of what they’re doing – they’re unaware of sitting closer, facing the food, chewing less, and so on,” say Brian Wanink, lead author of this study and of the book “Mindless Eating: Why We Eat More Than We Think.”

The study was published in the journal Obesity and includes observations of 213 diners at 11 all-you-can-eat Chinese restaurant buffets across the country.  Study participants included a range of normal weight to obese diners, none of whom were Asian.  Major study findings include:

* 27% of normal-weight patrons faced the buffet compared to 42% of obese diners.

* Overweight diners sat an average of 16 feet closer than normal-weight diners.

* 16% of obese diners sat at a booth rather than a table compared to 38% of normal weight diners

* 71% of normal-weight diners browsed the buffet before serving themselves compared to 33% of obese diners

* 24% of normal-weight people used chopsticks compared with 9% of overweight people

“When food is more convenient people tend to eat more,” say coauthor Collin R. Payne, New Mexico State University.

“These seemingly subtle differences in behavior and environment may cause people to overeat without even realizing it.”

An overload of calories throws critical portions of the brain out of whack, reveals a study in the October 3rd issue of the journal Cell, a Cell Press publication.  That response in the brain’s hypothalamus—the “headquarters” for maintaining energy balance—can happen even in the absence of any weight gain, according to the new studies in mice.

The brain response involves a molecular player, called IKKß/NF-?B, which is known to drive metabolic inflammation in other body tissues.  The discovery suggests that treatments designed to block this pathway in the brain might fight the ever-increasing spread of obesity and related diseases, including diabetes and heart disease.

“This pathway is usually present but inactive in the brain,” said Dongsheng Cai of the University of Wisconsin-Madison.  Cai said he isn’t sure exactly why IKKß/NF-?B is there and ready to spring into action in the brain.  He speculates it may have been an important element for innate immunity, the body’s first line of defense against pathogenic invaders, at some time in the distant past.

” In today’s society, this pathway is mobilized by a different environmental challenge—overnutrition,” he said.  Once activated, “the pathway leads to a number of dysfunctions, including resistance to insulin and leptin,” both important metabolic hormones.

Earlier studies showed that overnutrition can spark inflammatory responses in the peripheral metabolic tissues, including the muscles and liver, and therefore cause various metabolic defects in those tissues that underlie type 2 diabetes.  As a result, scientists identified IKKß as a target for an anti-inflammatory therapy that was effective against obesity-associated diabetes.

Yet whether metabolic inflammation and its mediators played a role in the central nervous system remained uncertain.  Now, the researchers show that a chronic high-fat diet doubles the activity of this inflammatory pathway in the brains of mice.  Its activity is also much higher in the brains of mice who are genetically predisposed to obesity, they found.

The researchers report that that increased activity of the IKKß/NF-?B pathway can be divorced from obesity itself -infusions of either glucose or fat into the brains of mice alone led to this inflammatory brain reaction.

Further studies revealed that this activity in the brain leads to insulin and leptin resistance.  Insulin lowers blood sugar by causing cells of the body to take it up from the bloodstream.  Leptin is a fat hormone important for appetite control.

Moreover, the researchers found that treatments preventing the activity of IKKß/NF-?B in the animals’ brains protected them from obesity.

While chronic inflammation is generally considered a consequence of obesity, the new results suggest the inflammatory reaction might also be a cause of the imbalance that leads to obesity and associated diseases, including diabetes.  As Cai says, it appears that inflammation and obesity are “quite intertwined.”  An abundance of calories itself promotes inflammation, while obesity also feeds back to the neurons to further promote inflammation in a kind of vicious cycle.

The findings could lead to treatments that might stop this cycle before it gets started.

“Our work marks an initial attempt to study whether inhibiting an innate immune pathway in the hypothalamus could help to calibrate the set point of nutritional balance and therefore aid in counteracting energy imbalance and diseases induced by overnutrition,” the researchers said.  “We recognize that the significance of this strategy has yet to be realized in clinical practice; currently, most anti-inflammatory therapies have limited direct effects on IKKß/NF-?B and limited capacity to be concentrated in the central nervous system.  Nonetheless, our discoveries offer potential for treating these serious diseases.”

If realized, such a strategy would likely offer a safe approach given that the critical pathway appears to be unnecessary in the hypothalamus under normal circumstances, they noted.

A carefully framed combination of moderate exercise and nutritional supplements could help older people maintain an active lifestyle for longer.

A Manchester Metropolitan University study has found that taking carbohydrate and protein supplements just before and just after low-resistance exercise could boost muscle performance and slow muscle wastage in people over retirement age.

Moreover, this combination appears to deliver greater fitness benefits than undertaking heavy-resistance training with or without changing one’s nutritional habits.

This was the first-ever study of the combination of structured exercise and nutritional supplements to focus wholly on older people.  Undertaken as part of the SPARC (Strategic Promotion of Ageing Research Capacity) initiative, the findings will be discussed at this year’s BA Festival of Science in Liverpool on Thursday 11th September.  SPARC is supported by the Engineering and Physical Sciences Research Council (EPSRC) and the Biotechnology and Biological Sciences Research Council (BBSRC).

This groundbreaking study involved a carefully selected sample of around 60 healthy, independent-living adults aged 65 and over.

The volunteers were randomly divided into groups who underwent different 12 week programmes of physical exercise and nutritional supplementation.  Everyone was then re-assessed at the end of the programme.

Some groups undertook low-resistance exercise once a week; others undertook high-resistance exercise twice a week.  Within each group, some of the volunteers took protein and carbohydrate supplements while others did not.

When all the participants were re-assessed at the end of the 12 week programme, it was observed that muscle size and strength had increased in all groups.

However, the results suggested that older people would derive the most benefits if they took appropriate supplements coupled with low-intensity exercise.

“Maintaining muscle performance and arresting muscle wastage can offer older people real improvements in their quality of life,” says Dr Gladys Pearson, who led the research.  “Though we still need to assess precisely what level of exercise gives the best results, we believe we’ve shown that regular low-resistance exercise complemented by the right nutritional supplements could boost the well-being of the UK’s ageing population.”

Dr Pearson and her team now aim to look at the effectiveness of novel combinations of strength training and nutritional supplementation as a way of speeding recovery and improving mobility for old and young orthopaedic surgery patients.

However much the likes of Jamie Oliver or Gordon Ramsay might want to shake up our diets, culinary evolution dictates that our cultural cuisines remain little changed as generations move on, shows new research, published today, Thursday, 10 July, 2008, in the Institute of Physics (IOP)’s New Journal of Physics (NJP).

The research, ‘The non-equilibrium nature of culinary evolution’, shows that three national cuisines British, French and Brazilian – are affected by the founder effect which keeps idiosyncratic and nutritionally ambivalent, expensive and sometimes hard to transport ingredients in our diets.

Using the medieval cookery book, Pleyn Delit, and three authoritative cook books from Britain, France and Brazil, the New Penguin Cookery Book, Larousse Gastronomique and Dona Benta respectively, the researchers from the University of Sao Paulo, Brazil, compiled statistics which could be compared to see how time and distance effect the three different national cuisines.

Time, the number of ingredients used, the number of recipes published in each cook book and the ratio between the number of ingredients and the number of recipes in the books were used as variables to assess how our diets have evolved.

Three editions of Dona Benta, from 1946, 1969 and 2004, were evaluated to see how the Brazilian diet has changed over the past half century, amidst the change from a regional to a more globalised food consumer profile, and found that the rank and importance of certain idiosyncratic ingredients, such as chayote, an edible plant that is a frequent ingredient in Central and South American diets, remained much the same.

Ranking the importance of certain food types by their frequency of use in each national cuisine and comparing them to ingredients which have an equivalent rank in one of the other two foreign cuisines led to patterns emerging which suggest that all our menus evolve in similar ways.

So, whether it’s the Irish with potatoes, the French with frogs’ legs, the Germans with sauerkraut, the Ghanaians with plantains or the Japanese with fish stock, it seems a global food culture has not shifted some die-hard culture-based eating habits.

As the authors, from the Department of Physics and Mathematics at Sao Paulo University, write, “Some low fitness ingredients present in the initial recipes have a strong difficulty of being replaced and can even propagate during culinary growth.  They are like frozen “cultural” accidents.”

Individuals who are obese are at increased risk of many diseases, including type 2 diabetes and heart disease.  As 75%-95% of previously obese individuals regain their lost weight, many researchers are interested in developing treatments to help individuals maintain their weight loss.  A new study, by Michael Rosenbaum and colleagues, at Columbia University Medical Center, New York, has provided new insight into the critical interaction between the hormone leptin and the brain’s response to weight loss.

Leptin levels fall as obese individuals lose weight.  So, the authors set out to see whether changes in leptin levels altered activity in the regions of the brain known to have a role in regulating food intake.  They observed that activity in these regions of the brain in response to visual food-related cues changed after an obese individual successfully lost weight.  However, these changes in brain activity were not observed if the obese individual who had successfully lost weight was treated with leptin.  These data are consistent with the idea that the decrease in leptin levels that occurs when an individual loses weight serves to protect the body against the loss of body fat.  Further, both the authors and, in an accompanying commentary, Rexford Ahima, at the University of Pennsylvania School of Medicine, Philadelphia, suggest that leptin therapy after weight loss might improve weight maintenance by overriding this fat-loss defense.

“Consumers who understand their emotional ability can make higher quality consumption decisions such as health decisions and product choices,” explain the authors, Blair Kidwell, David M. Hardesty, and Terry L. Childers (University of Kentucky). “A person can know a lot about nutrition and know what foods are not healthy, but can still make poor decisions when unable to recognize, reason, and solve problems based on emotional patterns,” they add. For example, compulsive eaters may understand nutrition, but they may not realize their emotions affect their food choices.This research establishes a new method for assessing consumers’ emotional intelligence. The authors developed a scale by testing undergraduates with more than 110 questions about emotions and consumption. As a result of this research, the authors were able to determine which emotion-related questions best predicted overeating.

The researchers then narrowed the questions to 18. They measured four different dimensions of consumer emotional ability: perceiving, facilitating, understanding, and managing emotions.  This 18-item scale—called the CEIS, or Consumer Emotional Intelligence Scale—is a highly reliable indicator of consumer behavior.

It seems consumers who care about healthy eating need to consider their feelings instead of studying nutrition labels.