Leptin, the Appetite Hormone, Rewires the Brain

reposted from: http://www.genomenewsnetwork.org/articles/2004/04/16/leptin.php
search keywords: leptin, appetite, Leptin: wikipedia

Leptin, the Appetite Hormone, Rewires the Brain

By Nancy Touchette

Posted: April 16, 2004

Mice without the leptin gene are morbidly obese (right) compared to normal mice (left). Image courtesy Sebastien Bouret/University of Oregon.

Researchers have discovered that leptin, an appetite-suppressing hormone, works in an unexpected way. The hormone, which has attracted considerable attention as a potential key to weight loss, is produced by fat cells, but it controls hunger by acting on the brain. Now, two new studies in mice show that the hormone works by actually rewiring the neural circuits in the brain.

The research also shows that some of these circuits are set just after birth, presenting the possibility that, at least to a certain extent, the tendency to overeat and gain weight may be hardwired early in life.

Although the new studies were conducted in mice, researchers believe the research may help them understand human obesity because the hormone has the same effect in humans as in mice. Like mice, people who are missing the leptin gene become morbidly obese. But when these rare individuals are given leptin, they lose weight.

Most obese people are not missing the leptin gene and are known to produce leptin. In fact, some have more than enough. Researchers believe that obesity may be caused, in part, by defects in the signaling pathways in the brain that normally respond to leptin.

“We decided early on that the leptin story was going to very complicated,” says Jeffrey Friedman of Rockefeller University in New York City, who led one of the studies. “To move ahead, we have to understand how leptin acts normally and which of its effects are missing in obese individuals.”

Leptin promotes the growth of mouse neurons. Images show growth patterns without leptin (top) and with leptin. Image courtesy Science.

The findings surprised researchers, who thought that leptin worked by activating individual neurons, not by changing the way they connect to each other.

“You can imagine that information flows between neurons much like water through the plumbing system in a house,” says Friedman. “You can regulate this flow by opening and closing valves, or you can add or subtract pipes from the whole system.”

“We thought leptin would act by opening and closing valves. Instead, it appears to add and subtract pipes,” he says.

In the new study, published in Science, Friedman, in collaboration with Tamas L. Horvath at Yale University School of Medicine in New Haven, Connecticut, found that mice without the leptin gene have more connections coming into neurons affected by leptin than do other mice. The result was more circuits that increase appetite—and fat mice.

But when the mice were given leptin, the circuitry was reversed. The mice developed normal neural connections, and normal appetites.

In a second study, also appearing in Science, researchers noted that shortly after birth, both mice and humans experience a surge in leptin levels. This seemed perplexing because leptin normally signals appetite suppression. But newborns need to eat more, not less.

“People didn’t understand this leptin surge,” says Richard Simerly of the Oregon National Primate Research Center in Beaverton, who led the second study. “But we wondered if it was acting as some sort of developmental signal.”

Simerly and his colleagues found that in mice without the leptin gene, the neurons that normally respond to leptin fail to project to other regions of the brain involved in food intake—and the mice become fat.

When Simerly gave the mice leptin immediately after birth, all the neural circuits that control food intake formed normally and the mice maintained normal weight.

However, if the leptin-deficient mice were not given leptin until adulthood, the circuitry was not restored and the mice remained fat.

“We were stunned by this result,” says Simerly. “It told us that leptin acts as a developmental signal that determines the circuits that it acts on later in life.”

Taken together, the two studies suggest that leptin affects two distinct types of neural connections at different times. Early in life, leptin guides output from neurons that affect appetite. Later, leptin signals the input to these same neurons.

Researchers still don’t know what causes the surge in leptin during development or whether it is affected by early feeding habits.

If leptin release in early life is influenced by nutrition, this period could be critical in future weight control.

It’s not yet clear whether the neurons that affect appetite in mice work the same way in humans. But the studies raise the possibility that leptin affects the wiring of a brain circuitry that influences an individual’s weight for life.

“I wouldn’t exactly say that leptin dictates a ‘set weight’” says Simerly. “But in controlling the kinds of neural connections that are made in the brain, leptin may be one of the factors that determines the range of weights a person is likely to have throughout life.”

Pinto, S. et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304, 110-115 (April 2, 2004).

Bouret, S.G. et al. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 110-115 (April 2, 2004).

Elmquist, J.K. and Flier, J.S. The fat-brain axis enters a new dimension. Science 304, (April 2, 2004).

crabsallover weight

reposted from: hackers diet.

4 May 2009 - my BMI 26.2

Fine Tuning body weight

reposted from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2582659

I googled: fine tuning body weight, because I'm curious to know how the body fine tunes body weight maintenance. As the article states "Although it is true that weight gain occurs when food intake exceeds energy expenditure, it is important to note that even a 1% mismatch between the two can lead to a substantial weight gain after only a few years." 1% of 2000 calories/day = 20cals/day x 365 days = 7300 cals per year. 3500 cals excess results in one pound increase. So 7300 cals excess = 2 pounds increase per year = 20 pounds over 10 years.

Could there be a fine-tuning role for brain-derived adipokines in the regulation of bodyweight and prevention of obesity? by Russell E. Brown

Abstract: "The body appears to balance energy metabolism via an endogenous lipostatic loop in which adipose stores send hormonal signals (e.g. adipokines such as leptin) to the hypothalamus in order to reduce appetite and increase energy expenditure. However, the brain is also a novel site of expression of many of these adipokine genes. This led to the hypothesis that hypothalamic-derived adipokines might also be involved in bodyweight regulation by exerting some effect on the control of appetite or hypothalamic function." ... Although adipokines secreted by adipose tissue appear to the main regulator of lipostatic loop, this review shows that the fine tuning that is required to maintain a stable bodyweight by this system might be accomplished by hypothalamic-derived adipokines. Perturbations in this central adipokine system could lead to alterations in normal hypothalamic function which leads to unintended weight gain."

Crabsallover Summary: Adipokines derived from the brain (hypothalamus) might control the reduction of appetite and increase energy expenditure, in addition to Adipokines derived from fat (adipose) tissues.

Prof. Lesley Regan exposes the Diet Industry

reposted from: http://www.bbc.co.uk/iplayer/episode/b00jz1kq/Professor_Regans..._Diet_Clinic/

All sensible scientific stuff. Eat a healthy diet, take care to not eat too much (no calorie excess) and exercise. The rest of the diet industry is baloney!


Over a third of us are overweight and we spend 11 billion pounds a year trying to get thin. Professor Regan takes on the multi-million pound diet industry. Using herself as a guinea pig, she will discover what to eat to lose 10lbs a year, find a diet pill that actually works, investigate whether we should all be taking vitamins to supplement our diets, and uncover a low-fat product that can really be trusted.

Along the route to ultimate weight loss, she discovers that her body is 25 per cent fat, and takes on the diet pills you can buy on the high street by designing her own - with extraordinary results. Over 70 per cent of the study participants lose weight in just a month.

She also puts her taste buds to the ultimate test in one of the world's leading food labs, and chews her way through a mound of carrots. The raw carrot is billed as the ultimate health food, but in this rather unusual experiment with the world's first computerised stomach model, Professor Regan discovers the raw carrot is not all it is cracked up to be.

Broadcast on:
BBC Two, 11:30pm Tuesday 21st April 2009
Duration:
60 minutes
Available until:
8:59pm Thursday 14th May 2009

Go to Professor Regan's... site

The five ages of the brain: Old age

reposted from: http://www.newscientist.com/article/mg20227023.100-the-five-ages-of-the-brain-old-age.html?DCMP=OTC-rss&nsref=online-news

• 06 April 2009 by Helen Thomson
• Magazine issue 2702. Subscribe and get 4 free issues.
• For similar stories, visit the The Human Brain Topic Guide

Read about all five ages of the brain in our special feature

Down but not out

By the time you retire, there's no doubt about it, your brain isn't what it used to be. By 65 most people will start to notice the signs: you forget people's names and the teapot occasionally turns up in the fridge.

There is a good reason why our memories start to let us down. At this stage of life we are steadily losing brain cells in critical areas such as the hippocampus - the area where memories are processed. This is not too much of a problem at first; even in old age the brain is flexible enough to compensate. At some point though, the losses start to make themselves felt.

Clearly not everyone ages in the same way, so what's the difference between a jolly, intelligent oldie and a forgetful, grumpy granny? And can we improve our chances of becoming the former?

Exercise can certainly help.

Numerous studies have shown that gentle exercise three times a week can improve concentration and abstract reasoning in older people, perhaps by stimulating the growth of new brain cells. Exercise also helps steady our blood glucose. As we age, our glucose regulation worsens, which causes spikes in blood sugar. This can affect the dentate gyrus, an area within the hippocampus that helps form memories. Since physical activity helps regulate glucose, getting out and about could reduce these peaks and, potentially, improve your memory

(Annals of Neurology, vol 64, p 698).

Coordination training could also help. Studies have shown that specifically targeting motor control and balance improves cognitive function in 60 to 80-year-olds. A few sessions on the grandchildren's Nintendo Wii could bring similar benefits.

If you're struggling to find the guitar hero in yourself, however, try a cognitive workout instead.

"Brain training" was once considered flaky, but a study due to be published in the Journal of the American Geriatrics Society in April concludes that computerised brain exercises can improve memory and attention in the over 65s.

Importantly, these changes were large enough that participants reported significant improvements in everyday activities, such as remembering names or following conversations in noisy restaurants.

Avoiding the grumps is even easier. Dopamine receptors - responsible for feelings of positive emotions - are in decline, with the potential to cause depression, but you can give yourself a regular dose of dopamine by eating certain foods, such as yoghurt, almonds and chocolate.

In fact, your brain is doing it all it can to ensure a contented retirement. During the escapades of your 20s and 30s and the trials of midlife, it has been quietly learning how to focus on the good things in life. By 65 we are much better at maximising the experience of positive emotion, says Florin Dolcos, a neurobiologist at the University of Alberta in Canada. In experiments, he found that people over the age of 60 tended to remember fewer emotionally negative photographs compared with positive or neutral ones than younger people (Psychological Science, vol 20, p 74).

When I was young...

MRI scans showed why. While the over-60s showed normal activation in the amygdala, a region of the brain that processes emotion, its interaction with other brain areas differed: it interacted less with the hippocampus than in younger people and more with the dorsolateral frontal cortex, a region involved in controlling emotions. Dolcos suggests that this may be a result of more experience of situations in which emotional responses need to be kept under control. Older people really do see the world through rose-tinted glasses.

So while nobody wants to get older, it's not all doom and gloom. In fact you should probably stop worrying altogether. Studies show that people who are more laid back are less likely to develop dementia than stress bunnies. In one study, people who were socially inactive but calm had a 50 per cent lower risk of developing dementia compared with those who were isolated and prone to distress (Neurology, vol 72, p 253). This is likely to be caused by stress-induced high levels of cortisol, which may cause shrinkage in the anterior cingulate cortex, an area linked to Alzheimer's disease and depression in older people.

So while our brains may not wrinkle and sag like our skin, they need just as much care and attention - so don't give up on yours too soon. When you notice the signs of age, go for a walk, do a crossword and try to have a laugh - it might just counteract some of the sins of your youth.

Read about all five ages of the brain in our special feature