How the Stomach Talks to the Brain
By Willow Lawson, Publication Date: September 2, 2003
Summary: A chemical messenger tells us when the belly needs filling. Ghrelin (pronounced GRELL-in), discovered only a few years ago, stimulates our 'need to feed' even in cases where the belly is full.
It's supposed to be simple: you eat when you're hungry and stop when you're full.
It is, of course, much more complicated than that. As the rate of obesity demonstrates, one's appetite stems from more than an empty stomach or a need for nutrients. Humans are built to be susceptible to super-sizing and that second slice of pie. Studies have shown that given the opportunity, most of us will eat when we are not hungry. Give us a bigger portion and we'll polish it off.
This isn't surprising, given that humans evolved to pack on a few extra pounds in preparation for future shortages. But what has surprised scientists who study appetite are the many subtle influences on when and what we eat. In recent years, scientists have learned the urge to eat is governed largely by an elaborate ricochet of hormones - among the dozens are leptin and insulin -- that shuttle between the gut and brain.
"Everyone used to think it was so silly that the stomach might talk to the brain," says John Morley, M.D., a professor of gerontology at the St. Louis School of Medicine, whose research gives new meaning to "gut instincts." Morley has been studying the tendency for the elderly to lose the desire to eat. "It makes sense that if you're stomach's empty, it wants to tell the brain."
But whether the stomach is empty of full may not even matter. One of these chemical messengers, ghrelin (pronounced GRELL-in), discovered only a few years ago, stimulates our "need to feed" even in cases where the belly is full.
Give a person a shot of ghrelin and they develop a ferocious hunger. Levels increase during fasting and before meals and fall off after eating. Secreted by endocrine cells in the stomach and small intestine, ghrelin circulates in the bloodstream and stimulates the brain and the pituitary gland to release other hormones, possibly growth hormone, affecting metabolism and the cardiovascular system.
Ghrelin levels rise in people who have lost weight and may be the reason dieters have trouble keeping their weight down for the long term. However, a recent study in The New England Journal of Medicine showed that ghrelin decreases in people who have undergone gastric bypass surgery to lose weight. These people often report feeling less hungry after the operation.
Such findings are often heralded in the news as the breakthrough that will lead to a cure for obesity. Several drug companies are working on it, hoping to be the ones to capitalize on a miracle pill. But Morley says we have a lot to learn about appetite before we can even contemplate new therapies for people who are overweight. Researchers are still debating the many ways that ghrelin seems to affect the body.
"People get excited because they see one effect [of a hormone] and don't see the others until later," he says. And there are always side effects. Ghrelin seems to affect memory formation as well, says Morley, a mechanism that is not yet understood.
Ghrelin's first use in medicine will likely be to stimulate appetite in anorexics and in the elderly, says Morley. "I'm tremendously cynical about obesity drugs."
He is emphatic that people should not hope that a cure for obesity is around the corner. "The only way to combat obesity is exercise," he says. "It's very simple." He points to the many studies that show exercise does more than keep a person at a healthy weight. "There's more and more data that shows exercise helps us think better, feel better and fight depression. Yet we are trying to find a way to avoid something that'd good for us."
Catabolic wasting or cachexia is a clinical wasting syndrome that is characterized by unintended and progressive weight loss, weakness, and low body fat and muscle. At least 5% of body weight is lost. Cachexia is not caused by poor appetite and nutritional intake, but rather by a metabolic state in which a "breaking down" rather than a "building up" occurs in bodily tissues no matter how much nutritional intake occurs. Additionally, whether a patient receives nutrition orally or intravenously makes no difference. The patient simply cannot gain weight, so eating more is not an answer.
It is estimated that half of all cancer patients experience catabolic wasting, with a higher occurrence seen in cases of malignancies of the lung, pancreas, and gastrointestinal tract. The syndrome is equally common in AIDS patients and can also be present in bacterial and parasitic diseases, rheumatoid arthritis, and chronic diseases of the bowel, liver, lungs, and heart. It is usually associated with anorexia and can manifest as a condition in aging or as a result of physical trauma. Catabolic wasting is a symptom that diminishes the quality of life, worsens the underlying condition, and is a major cause of death.
Cachexia and Cancer
Researchers previously believed that cancer increased metabolic demand (stolen protein), produced toxins, and suppressed appetite, resulting in malnutrition. New research, however, shows that although cancer may raise resting metabolic rate, improved nutrition does not alleviate the symptoms of anorexia, chronic nausea, early satiety, and changes in taste that make even favorite foods unpalatable to some cancer patients. The view of clinicians is that bodily wasting is the result of a combined action of tumor products and host immune factors--in particular, cytokines--that lead to poor appetite, muscle wasting, and an altered metabolism. The cytokines interleukin-1 (IL-1), IL-6, interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), and brain-derived neurotrophic factor appear to increase and play a role in the progression of cachexia in cancer, as well as in other diseases associated with bodily wasting.
Other metabolic alterations associated with the syndrome are hyperglyceridemia, lipolysis, and accelerated protein turnover, all leading to a loss of fat mass and body protein. The dysregulation of metabolic processes produces a negative energy balance.
Clinicians are currently treating cancer-related catabolic wasting with a variety of interventions, including nutritional supplementation, administration of cytokine inhibitors, steroids, hormones, cannabinoids, and thalidomide. Gemcitabine, a chemotherapeutic drug, has shown clinical benefits in treating cachexia. Newer nutritional intervention with megestrol acetate derivatives, gamma-receptor agonists, amino acid manipulations, myostatin inhibitors, and uncoupling protein modifiers is currently being explored. Further research must be done to investigate gender differences in relation to pathophysiology and therapy.
There is some evidence that the drug hydrazine sulfate may help cancer patients gain weight and improve the cachectic state. The drug is by prescription and should be given by a complementary physician familiar with its use, as it can be toxic. The dose is usually 60 mg a day. Narcotic painkillers or benzodiazepine anxiety-reducing agents cannot be given concomitantly.
Cachexia and HIV
Bodily wasting is a common manifestation of HIV, occurring at any state of infection and indicative of disease progression. Malnutrition, a result of appetite loss, is commonly due to nausea and vomiting. Weakness and diarrhea are often present as well. Persons with HIV may also experience malabsorption of nutrients due to enteric infections associated with the disease, even if they consume sufficient calories.
The effects of malnutrition are thought to contribute to increased immune suppression including a reduction in T-lymphocyte helper and suppressor cells, altered phagocytic functions, and decreased killer-cell activity, leading to opportunistic infections and cancers. Proinflammatory cytokines IL-1, IL-6, and TNF have been cited in many studies as potential causes of wasting. Most people with advanced HIV and AIDS have some degree of wasting.
To reverse weight loss, appetite stimulants, anabolic agents (such as growth hormone or testosterone), cytokine inhibitors, and hormones are often prescribed. Megestrol acetate and dronabinol (which contains the active ingredient in marijuana) are approved for the treatment of wasting. Thalidomide, which aids in the healing of aphthous ulcers of the mouth and esophagus, is now available.
Unfortunately, the cachectic state is all too apparent to any observer. In severe chronic disease with the development of multiple organ failure, some degree of malabsorption of nutrients probably contributes to the cachectic state. The entire picture is reflected in a continuing decline of the serum albumin as the illness progresses. Conversely, an increase in serum albumin suggests an improvement in the nutritional state. As long as a patient is maintained on nutrition by the normal route (by mouth), optimizing the state of digestive secretions is probably advisable, although there may not be clinical studies demonstrating this. The Heidelburg test reflects this environment and can be used to ascertain the need for either hydrochloric acid or pancreatic enzyme supplementation.
Advanced Viral Research Advanced Viral Research cordially invites shareholders to meet the new cordially invites shareholders to meet the new CEO Dr. Elma Hawkins.
When: Monday June 21, 2004 Time: 5:00-7:00 PMWhere: New York Academy of Sciences2 East 63rd St., New York, NY 10021Contact: Ronnie or Kelly at 508-222-4802
(Voluntary Disclosure: Position- Long; ST Rating- Strong Buy)
Too bad the the AVR118 abstract
says little to nothing about "muscle wasting", and only addresses a minimal
amount of "fat gain".....And, Oh Yea, it makes you "feel good'....
where is Bill Bregman to tell us of
the many "surprises" at the ASCO presentation. better yet, the mysterious
"China" connection lol. goooooo advr
(Voluntary Disclosure: Position- Long)
Novel idea: An ADVR Question...
I thought I might bring a quick change of pace to the board and ask an ADVR question...
We still have 2 more payments from the Dickey's coming in which should take us through the end of the year at a minimum if my understanding is correct.
What event is left out there that would affect the pps?? In each of your opinions, how far do we slide, and what piece of news would stop the slide and cause a fairly substantial rise in pps?
Just funded my brokerage account today, and I'm wondering if I should dollar cost average down, or if I should look elsewhere...
Thanks for your responses...
(Voluntary Disclosure: Position- Long; ST Rating- Strong Buy; LT Rating- Strong Buy)
"Just funded my brokerage account
today, and I'm wondering if I should dollar cost average down, or if I
should look elsewhere..."
Good to see you back, Spoilerdave. Missed you!
Both options have merit. I like the averaging down.
Yet, if we don't hear of anything really substantial regarding more up-to-date info on our trials, or some concrete partnering possibilities, or at LEAST some media coverage discovering us as an upcoming Biotech with great possibilities...welllllll, then, we can all just sit here and wait, and hope, and we better be patient....for a long time.
Dave- ADVR has a legacy of
Not all of it shareholder welcomed, but
ADVR has survived and managed.
Currently they appear to have more going for them in terms of progress than ever before, to include getting peer recogniton.
My opinion is that advr will continue to survive financially.
It is a given that they will need money to fund a large and
advanced trial for 118.
I hope they do not issue more shares to raise the money
SO- Imo on one hand thats a possibility
On the other--RESULTS RESULTS RESULTS when finally and completely in could garner another "dickie " deal from
whomever OR a deal with a Pharma or biotech[ may be too
early for that] Possible deal with a Dana Farber like
I do believe that this company will sustain itself and that they do have a potential platform with 118-
It will take a lot of time and money though
Short term if there is no new news or institutional interest
from the street per the CEOs efforts to tell the story
I see ADVR going back to the single digit area
Thanx for the responses everyone...
Every once in a while I like to get a pulse on everyone's sentiment. I thought ASCO had big potential, and maybe it sparked some interest that we won't even know about for a year or more...
I'd like to think that AVR118, Product R, or Reticulose whatever they decide to call it this week has potential, but there has to be some way to get this approved and on the market...
I've owned this sucka since 1996 and I'm just tiredly waiting for something resembling organization. This should have been on the market long ago...
I've bought and sold and mostly lost, always remembering that one day in 96 when it topped $1.75 for a heartbeat, but I didn't have enough shares to buy a skateboard. If it did that again today, I'd be able to sell out and buy a house...
So here I wait... patiently for it to top a quarter so I can double my money...
Someday... over the rainbow...
Thanks again for your thoughts...
(Voluntary Disclosure: Position- Long; ST Rating- Strong Buy; LT Rating- Strong Buy)
ADVR PRICE TARGET LOWERED BY BARRY
Barry-- I will ALERT YOU
Ok Mosquito ?
you sure have faith in advr
are you going to CACKLE now for your Klown friend