The right time for a women to diet?

25 April 1992 by LEIGH DAYTON , SYDNEY

Women who diet during the second half of their menstrual cycle will find it an uphill struggle, according to an Australian scientist. Philippa Wall of the University of Sydney says that in the last two weeks of a woman’s cycle, natural hormonal changes cause a surge in appetite. Women who diet will therefore find it easier if they confine the diet to the two-week period that begins with menstruation.

The cyclical ebb and flow of appetite also helps to explain why many women gain weight after the menopause or when they are taking birth control pills, says Wall. Such women do not experience a hormonally triggered cycle of increased and decreased appetite throughout the month and eat slightly more than women who have this ‘internal rhythm’, she argues.

Fat rats – a high fat diet makes you fat forever

12:33 07 November 2000 by Helen Phillips, New Orleans

A fault in the blood vessels of the brain may be one cause of obesity, say researchers in Germany.

Heike Nave from Hannover Medical School and her colleagues found that a small number of obese rats had a damaged blood-brain barrier.

Normally the barrier tightly controls what passes from the blood into the brain, but in obese rats the barrier was breached in two specific brain regions. This may interfere with the brain’s uptake of an appetite-suppressing hormone, the researchers believe.

Nave and her colleagues initially thought that the damage might alter the way the appetite-control hormone leptin passes into the brain. But they found equivalent leptin levels in the brains of obese and lean animals.

Instead, they believe that the damaged membranes of the capillary walls result in a loss or masking of the leptin receptors, the receiving sites for the hormone.

Leptin is released by fat cells and normally travels in the blood to the brain, where it acts mainly in the cortex and hypothalamus. These are precisely the brain regions where the blood-brain barrier is breached, says Nave.

The obese mice had no genetic defect that could have caused the damage to the barrier directly. They had simply been fed a high-fat diet.

The researchers can’t yet say how a high-calorie diet could cause membrane damage. But once the process is started, the resulting lack of appetite suppression could plausibly lead to a cycle of overeating and further damage.

“It’s just four rats so far,” says Nave. “But this is just the first part of our study.”

This research was presented at a conference in New Orleans, organised by the US-based Society for Neuroscience. New Scientist’s full coverage of the conference is here: www.newscientist.com/conferences/

Stomach hormone turns hungry people into junkies

18:02 06 May 2008 by Ewen Callaway

Picture a fat slice of chocolate cake, its thick caramel glaze oozing onto a plate. Your brain, right now, is thinking just like a junkie’s, a new study suggests.

When volunteers received a dose of a natural hunger-inducing hormone called ghrelin, their brains responded to pictures of food in the same way that addicted people’s brains do to cigarettes or drugs, says Alain Dagher, a neurologist at McGill University in Montreal, Canada, who led the study.

This mechanism probably helped humans to load up on life-saving calories when food was scarce – a likely scenario during much of evolutionary history. But with well-stocked supermarkets and a fast-food outlet on every corner, such brain signals can make food addicts of us all.
Stimulant effect

Made in the stomach, ghrelin levels rise when people are hungry and wane after a meal. People who get injections of the hormone gorge themselves, while those suffering from a rare disease that keeps ghrelin levels unusually high tend to be obese overeaters.

“I think it’s the most powerful appetite stimulant that has ever been found,” Dagher says.

To test the hormone’s effect on the brain, his team gave a small dose to 12 people a few hours after breakfast. Then, the researchers scanned the subjects’ brains while they looked at pictures of pizza, hamburgers and other tempting foods. Dagher’s team compared the results to brain scans taken before volunteers received the dose of ghrelin.
Memory improvement

After receiving the hormone, the brains of volunteers resembled those of addicts looking to buy drugs. Dagher says. Seeing pictures of pizza and other treats sparked activity in several brain regions involved in decision-making and anticipating a payoff. The appetite-driving hormone made those connections stronger.

“It seems that ghrelin makes food appear more appealing,” he says.

The hormone also made food more memorable. Volunteers better recalled the food pictures after they got the hormone, and an area of the brain involved in memory lit up when subjects viewed images of food.

Several pharmaceutical companies already have their sights set on ghrelin, as drugs that block the hormone may quell hunger and fight obesity.
Mood changes

But they might have unintended behavioural side effects, as well, Dagher says. Meddling with ghrelin levels could alter the brain’s natural sense of rewards, potentially causing mood changes and even depression.

A diet drug called rimonabant that acts on a similar but separate brain system has been linked to depression and suicide, and although it is on sale in other countries, the US Food and Drug Administration has been slow to approve the pill.

But knocking out ghrelin could help scientists pick apart the hormone’s effects on the brain, says Matthias Tschop, an obesity expert at the University of Cincinnati.

“Does the pizza not smell that good anymore? Does the pizza not look as good anymore?” he adds.

Research in mice and rats suggests that the hormone changes how they see and smell food, and the same might be true in humans.

Study shows why poor prenatal nutrition leads to obesity

18:16 07 June 2005 by Anna Gosline

Poor nutrition in the womb may remodel the brain circuitry of newborn babies and predispose them to become obese in later life, research in mice suggests. The findings may help doctors to prevent the onset of obesity in susceptible infants who are born undernourished, say the researchers.

“Nutritional restriction during fetal life is not uncommon even in modern Western society,” says Norimasa Sagawa at Kyoto University Graduate School of Medicine, Japan, one of the researchers. “The important point is that after such nutritional stress during fetal life those (children) are exposed to high-calorie and high-fat diet during their later life.” A combination that may be a recipe for obesity.

Previous research has found that babies born to malnourished mothers are more likely to develop heart disease and diabetes in later life. These small babies have a phase of “catch-up” growth, where within their first months they grow more quickly than their bigger born counterparts, eventually reaching equal size. During catch-up, they also show elevated levels of the appetite-regulating hormone leptin. This is secreted by fat cells and acts to diminish appetite when reserves are high.

These children may have been pre-programmed with a “thrifty phenotype”, a term coined by David Barker at the University of Southampton, UK, and his colleagues. They reasoned that fetuses who sense food scarcity in the womb set their bodies to store more fat, more efficiently. But it was unknown exactly how this programming worked.
Feeding regimes

To investigate the mechanism behind this, a team led by Shigeo Yura, also at Kyoto University Graduate School of Medicine, gave pregnant mice different feeding regimes – normal and underfed.

As in previous studies, they found that underfed mothers gave birth to lower-weight pups that grew quickly and caught up with normal pups after 10 days. When fed a diet with an average calorific content after weaning, pups from both normally fed and underfed mothers weighed the same and had similar fat reserves.

But when the pups that experienced fetal impoverishment were fed a high-fat diet, they grew much bigger than pups that had prenatal plenty. At 17 weeks, mice from the underfed group weighed about 15% more and stored 50% more fat than the prenatally well-nourished mice on the same high-fat diet.

The underfed pups also showed a premature spike in leptin levels at 8-10 days old, compared with a surge on day 16 in normally fed pups. To test whether this early spike was the cause of later obesity, the team injected leptin into normally fed mice at 10 days. These mice also tended to become obese under calorie-rich diets, even though they had experienced no fetal malnutrition.
Always hungry

The authors conclude that the early leptin spike alters neural circuitry during a critical developmental window and interferes with the transport of leptin to the brain in adulthood. These changes effectively make the mice insensitive to “full” signals. Understanding this mechanism might help clinicians to reverse fetal programming, says Sagawa.

Susan Ozanne at Cambridge University, UK, who studies nutritional programming, cautions that it is difficult to translate these results from mice to humans, but she sees potential to treat obesity-prone children. “The evidence certainly suggests there are critical time periods in humans and there is some kind of postnatal plasticity where you have the potential to intervene.”

She adds that the results reinforce the importance of a balanced diet during pregnancy – not just the raw amount of calories. “You can have lots of food but still be starved in terms of a particular nutrient,” she says.

Some of us really are addicted to food

17:57 10 August 2007 by Roxanne Khamsi

A key appetite-suppressing hormone called leptin might limit hunger by making food appear less delectable. The finding provides more evidence that food addiction has a real biological basis and points to new ways to treat obesity, according to researchers.

This influence of leptin was discovered during brain scans of two teenagers who completely lack the hormone. Parts of their brains reacted more strongly to bland foods than the brains of people with the hormone, suggesting the hormone suppresses appetite by dampening our perception of how appetising certain foods are.

Under normal circumstances, our body’s fat cells churn out leptin, which travels through the blood to the brain where it reduces hunger. Studies suggest that the brains of obese individuals might become insensitive to the hormone.

Sadaf Farooqi at the University of Cambridge, UK, and her colleagues came across two obese teens with another problem: they have an extremely rare genetic disorder that prevents them from producing leptin in the first place. Farooqi says she knows of only 12 people in the world that have this congenital problem.
Broccoli craving

Without leptin, the two teens wanted to eat non-stop. The boy weighed 103 kilograms by age 14 and the girl weighed 128 kilograms at 19 years old. As part of the study, the researchers asked them to rate how much they liked various foods, ranging from chocolate cake to broccoli, and discovered that they rated bland foods unusually highly.

Using functional magnetic resonance imaging (fMRI) technology, they then observed how the teens’ brains responded to images of such foods.

Both the boy’s and girl’s brain responded similarly to the food images regardless of whether they had eaten or not. Moreover, the images provoked a strong reaction in the nucleus accumbens, a brain region thought to drive drug addiction. Healthy control subjects included in the study also had this brain response – but only on an empty stomach.

Farooqi then began treating the two leptin-deficient teens with the hormone and tested their brain response to various foods one week later. After receiving leptin therapy, the nucleus accumbens of the subjects only became activated by foods when they had not eaten for several hours.
Cake effect

The patients also changed their mind about bland foods such as broccoli and cauliflower, giving them a much lower rating than before. But they still rated cake and other goodies highly.

“Why it should be cake and not broccoli, we don’t know,” says Farooqi.

With long-term treatment, the teens no longer craved food non-stop and eventually slimmed down to a normal bodyweight. For example, after one year of receiving leptin, the boy weighed about 50 kilograms.

“The finding should encourage a more sympathetic attitude [towards] people with weight problems,” Farooqi says. An understanding that we have an in-built biological liking for certain foods may explain why some people are more prone to crave them.
The munchies

Leptin researcher Jenni Harvey at the University of Dundee, UK, says the new findings improve our understanding of the hormone’s influence. But she adds that other physiological pathways can influence how rewarded we feel by certain foods.

Signalling molecules such as cannabinoids, for example, also appear to manipulate our food cravings.

Farooqi notes that leptin might influence the brain indirectly by triggering a cascade of reactions. So while most obese individuals produce sufficient amounts of leptin, they might possess altered versions of other signalling molecules further along this pathway. As a result, leptin’s message might not get through to the brain.

Farooqi suggests that scientists should look to see if this is the case as it could point to new drug targets to fight obesity.

Hormone jab naturally reduces appetite

25 July 2005 by Rowan Hooper

A hormone jab may offer burger lovers and the obese a way of reducing their appetites like the turn of a dial. A team at Imperial College London, UK, have found a natural hormone that boosts the stomach’s “full” signal.

The hormone is oxyntomodulin, a peptide produced by the small intestine after a meal. In a trial, a group of 14 obese and overweight subjects self-administered doses of the hormone 30 minutes before breakfast, lunch and dinner. After four weeks they had lost an average 2.3 kilograms compared with a control group. The loss amounted to on average 2.4% of body weight.

“By giving the overweight subject oxyntomodulin we are fooling the brain, in a very natural way, into thinking it has just eaten a meal and is no longer hungry,” says Steve Bloom, who led the trials.

The researchers also found that the daily energy-intake by the test group was reduced by an average of 170 kilocalories after the first injection, to 250 kcal per day at the end of four weeks. The average recommended intake is 2500 kcal per day for men and 1940 kcal for women.

The test subjects’ leptin levels – a hormone responsible for regulating the body’s energy expenditure – were also reduced. The researchers also found a reduction in the levels of adipose hormones. These hormones normally encourage the build up of adipose tissues – where fat cells are stored.
Broad brain effects

Now a spin-off company is developing an analogue of the hormone and a “patient friendly” oral preparation, thus avoiding the need for self-injecting. It will be some years before anything is widely available, however.

Any treatment can hardly come soon enough, says Bloom. The health effects of obesity kill over 1000 people every week in the UK alone. In the US, over 65% of adults are overweight.

Bloom says that there were no significant side effects to the hormone injection during the trial and that patients did not develop tolerance to the effects of the hormone. Drugs currently being developed to combat obesity have broad effects on the brain so are more likely to have unwanted side effects, he adds.

“The big thing is that you have had an oxyntomodulin administration from your own gut switching off your hunger after a meal every day of life,” says Bloom. “This is the way you normally lose your appetite after a meal.”

He presented his findings at a meeting of the Physiology Society in Bristol, UK, on Friday.

Anorexia linked to mystery molecule

16:55 27 March 2003 by Shaoni Bhattacharya

Anorexic women have much higher levels of a mysterious molecule suspected to affect appetite, researchers have shown for the first time. The peptide, called CART, could be a candidate for new appetite-altering drugs, they say.

Levels of CART were 50 per cent higher in blood samples from anorexic women, compared with women without the eating disorder, says Sarah Stanley, an endocrinologist at Imperial College London. CART levels were also found to rise as the women’s weight fell.

However, the function of CART in humans is not known. “And because we know so little, it is difficult to know if CART is the cause of the weight loss or the result,” Stanley told New Scientist.

The team, based at Imperial College and the Eating Disorders Unit at London’s Maudsley Hospital, will now proceed with experiments giving CART to humans to see if it has a real effect on appetite.

“Understanding the biology of anorexia nervosa is terribly important and any chink of light that might be shed on it through molecular research is certainly worth pursuing,” says Stephen O’Rahilly, an expert in the molecular mechanisms of obesity at the Cambridge Institute for Medical Research, UK.
Up and down

CART is made in a variety of places in the human body including the brain, pituitary and adrenal glands. Studies in rats have linked the molecule to appetite. But CART both increases and reduces the appetite in rats, depending on which part of the brain it is injected into.

In the latest research, the team measured CART levels in the blood of anorexic women, anorexic women who were in the process of regaining weight, and recovered anorexic women who had maintained a normal body weight for a year. “We found a very, very strong correlation between plasma CART and body mass index,” Stanley says.

Next, as well as giving CART to people, the team plans to examine CART levels in obese patients and those who have lost their appetite because they have a malignant disease. CART could also be a possible target for obesity drugs if it proves to reduce appetite, says Stanley.

“CART is definitely expressed in the appropriate parts of the hypothalamus to be involved,” O’Rahilly told New Scientist. “But one should be cautious about leaping immediately to therapeutic applications.” For example, it is difficult to know if measurements of CART in the blood reflect the situation in the brain, he says.

The findings were presented at the British Endocrine Societies annual meeting in Glasgow, UK.

Artificial sweetener may reduce appetite

06 October 1990 by ALISON ABBOTT and PHYLLIDA BROWN
ASPARTAME, the artificial sweetener used in diet cola and many other products, may diminish people’s appetites, according to British researchers. This claim, made at a biochemistry conference, comes as a surprise to nutritionists who had believed that the sweetener had no biological activity other than its sweet taste.

Peter Rogers, from the Agricultural and Food Research Council’s Institute of Food Research in Reading, and John Blundell from the University of Leeds, gave aspartame in capsules to 16 undergraduates one hour before a sandwich lunch of 1200 kilocalories. Each capsule contained 200 milligrams of aspartame – equivalent to the amount in a can of diet cola. A control group took capsules containing no aspartame.

Before the meal, both groups felt equally hungry, according to standard psychological tests. However, the group that had taken aspartame ate 15 per cent fewer kilocalories than the controls, as measured by the amount of food left

Starving is like ecstasy use for anorexia sufferers

09:00 02 October 2007 by Alison Motluk
Anorexia and ecstasy use activate some of the same brain pathways, according to researchers who used mice to arrive at their conclusions. The findings hint that the condition works in a similar way to drug addiction, and may also point the way towards new drug treatments for the eating disorder.

Those diagnosed with anorexia nervosa restrict their food intake even though they may be in desperate need of energy. The condition has one of the highest mortality rates for any mental disorder, and there are few effective treatments currently available.

Valerie Compan at Centre National de la Recherche Scientifique (CNRS), Montpellier, France, is one of a growing number of researchers who believes that anorexia works in a similar way to addiction and that sufferers become “hooked” on the self-control involved.

After noticing that ecstasy (also called MDMA) use induces appetite suppression, she decided to investigate possible similarities further. Compan and colleagues focused on the nucleus accumbens, a reward centre in the brain with a high density of serotonin receptors – known as 5-HT4 receptors – that are known to play a role in addictive behaviour.
Addictive starving

The team stimulated these receptors in mice and found that this curtailed their urge to eat. The same stimulation also caused the release of a peptide known as CART. Elevated levels of CART have previously been detected following use of psychostimulant drugs, and at least one research group has found it in elevated levels among women suffering from anorexia.

In further experiments, Compan and her team injected mice with CART and also blocked it using RNA interference. Elevated levels of CART caused the animals to eat less and, conversely, lower levels increased their appetites.

Finally, to see if ecstasy-induced appetite suppression is mediated in the same way, the researchers gave the drug to mice engineered to lack 5-HT4 receptors. Unlike normal mice, these modified animals did not lose their appetites, suggesting the receptors do indeed control ecstasy’s appetite-suppressing effect.

Compan says that ecstasy and anorexia may have more in common than we think. Her study suggests that starving yourself can be addictive, and is further evidence that anorexia may be related to neurological defects.

The findings may also highlight targets for drug treatment. “Our studies over seven years open the possibility that the 5-HT4 receptor would represent an important therapeutic target to treat patients suffering from these disorders,” Compan says.

Memories of your last meal can help you stay thin

24 April 2008 by Colin Barras

Perhaps it really is possible to think yourself slimmer. Concentrating on a recent meal turns out to significantly reduce the desire to snack, suggesting that certain ways of thinking can curb your appetite.

Suzanne Higgs and colleagues at the University of Birmingham, UK, asked a group of women students to take part in a biscuit taste test, having previously given them a set lunch. Before the test began, Higgs encouraged half of the women to write a detailed description of their lunch, while the rest were asked to recall their journey to the campus.

After the taste test, which had been designed to hide the true nature of the study from participants, each woman was invited to eat their fill of the remaining biscuits. The women who had recalled their lunch ate fewer biscuits than those who recalled their journey, Higgs found.

The effect was small among the women who took the test 1 hour after eating, but became more noticeable as the day progressed. Of the women who took the test after 3 hours, those who actively recalled lunch had significantly reduced appetite compared with those who did not. Higgs suggests this is because after 1 hour the memory of eating lunch was still vivid enough to affect all the women’s appetites, regardless of what they were asked to recall. But after 3 hours the memory of lunch had faded, as had its influence on appetite – except for those women who boosted its effect by actively recalling what they ate (Physiology & Behavior, DOI: 10.1016/j.physbeh.2008.02.011).

“Other evidence suggests that thinking about food can actually increase subsequent intake, particularly in people who are dieting,” Higgs says. The key difference with her experiment, she suggests, is that subjects were asked to think about a specific meal and not a generic memory of food. This kind of vivid memory is replayed in the hippocampus, an area of the brain that might play an important role in decision-making as well as memory-processing. “One possibility is remembering recent eating boosts the influence this information has on decision-making,” she says.

This is in line with findings by Paul Rozin at the University of Pennsylvania, Philadelphia, who has studied patients with hippocampal damage. “Such folks will eat second and third lunches, so it makes some sense that activating the hippocampus might inhibit eating,” he says.

The relationship may also work in the opposite direction. “Recent research indicates that metabolic disorders associated with obesity impair hippocampal-dependent memory,” says Terry Davidson at Purdue University in West Lafayette, Indiana. “If these memory impairments promote obesity, then treatments that improve hippocampal-dependent memory function might have an anti-obesity effect.”

Whether a memory-boosting therapy is enough to beat obesity is another question, Susan Farr at the Saint Louis University Medical Center, Missouri, points out: “While a drug that acts in the hippocampus may be a good appetite regulator, it must also act in places like the hypothalamus, where appetite regulation also occurs.”