CHEMICAL COUPLE: The appetite-suppressing hormone hPYY hitches a ride with vitamin B-12 from the stomach to the bloodstream.
Image: Damian Allis, Syracuse University
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Losing weight is not always about anticipating swimsuit season or squeezing into skinny jeans—for the clinically obese, losing weight is about fighting serious illness and reclaiming health. But the primal part of the brain that regulates appetite will not place a moratorium on hunger just because someone and their doctor acknowledge the need to lose weight. Researchers at Syracuse University are working toward a unique solution: a stick of chewing gum that suppresses appetite.
There are many appetite-suppressing drugs on the market, a large number of which are based on stimulating amphetamines that carry the risk of serious side effects such as high blood pressure and heart failure. Syracuse Chemist Robert Doyle's research focuses on a hormone called human peptide YY (hPYY), which is released from cells that line the intestine whenever you eat and exercise. The more calories consumed, the more hPYY travels from intestinal cells into the bloodstream, eventually reaching the hypothalamus—an almond-size, evolutionarily ancient part of the brain that helps to regulate hunger, thirst, body temperature and sleep cycles.
Previous studies have shown that injections of hPYY suppress appetite in rodents, monkeys and people. In one study, both obese and lean people consumed about 30 percent fewer calories than usual at a buffet lunch only two hours after receiving a dose of hPYY.
Doyle wanted to know if hPYY still works when taken orally because pills and tablets are easy and painless compared with injections. The problem is that if you ingest pure hPYY, the caustic soup of acids and digestive enzymes in your stomach and intestine will destroy the hormone before it reaches your blood. In the body, intestinal cells secrete a precursor to hPYY that is transported into the blood and sliced into the right molecular shape in ways that are not well understood.
Doyle knew exactly how to protect hPYY in the stomach and gut. In earlier work, he found a way to safely ferry the hormone insulin through the digestive system by chemically linking insulin to vitamin B12. Since we do not produce B12 on our own, we have evolved a complex bucket brigade of molecules that ushers the essential vitamin on a journey from the food in our mouth to the bloodstream, where it nourishes all our cells. Doyle used this same trick with hPYY.
After bonding hPYY to vitamin B12, Doyle pumped a stream of the chemical couple directly into the stomachs of healthy rats. When he sampled the rats' blood for several hours after the feeding, he found levels of hPYY high enough to suppress appetite in a human adult. The findings show that B12 grants hPYY safe passage from the stomach to the bloodstream, as discussed online in the Journal of Medicinal Chemistry in November. Next, Doyle hopes to show that hPYY pumped into the stomachs of obese rats reduces their appetite and how many calories they consume.
The ultimate goal is hPYY medication that obese people can take orally in pill or tablet form—or even as chewing gum. Because recent research suggests there are PYY receptors in the tongue, hPYY chewing gum could promote feelings of satiety even sooner than hPYY pills.
Gregory Russell-Jones of Mentor Pharmaceutical Consulting in Sydney, who has saddled vitamin B12 with all kinds of peptides in the hopes of devising new drugs, says the new study "adds quite a bit of good work to the area. I think we are very close to oral delivery of peptides." Peptides are chains of amino acids, typically smaller than proteins, that function as hormones and signaling molecules in people and animals. They are small and chemically fragile enough to be destroyed by the stomach and gut but too large to pass into the blood unaided.
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8 Comments
Add CommentI'll eat my words if this 'ersatz' satiety project will ever work against obesity - it smacks of failure from the start; compare it with the high hopes hoisted on artificial sugar replacements which were found to cause an even greater addiction to sugary food!
Reply | Report Abuse | Link to thisLet's get real: only real food befitting our primatic body design can bring nutritional satisfaction.
I am speaking from experience, having lost one third of my body weight by simply eating more and more natural food, in the shape of apples, carrots, celery, oranges, tomatoes, and cabbage leaves - before ingesting anything else. For more information visit youthevity.com
Appetite suppression equals weight loss is the faulty paradigm of eat less, lose weight. When you eat less, your metabolism accomodates by slowing down to accommondate for the decrease in calories.
Reply | Report Abuse | Link to thisWeight management requires eating healthy foods: avoid sat fats and polyunsatruated fats which are hidden in processed foods and meats. There are also many other things that come into play involved in weight: genetic, cultural, metabolic, behavioral, and physiological factors. (NIH publicaton 98-4083.Nutrition education is a must. An excellent read on this is WHY WE GET FAT & WHAT WE CAN DO ABOUT IT by Gary Taubles(2011).
Sunny: Congrats on being able to eat lots of fruits and vegetables. Not everybody has the willpower to do that. Nor the money.
Reply | Report Abuse | Link to thisLN: Ask people who lose a hundred pounds or more after stomach surgery if a lower appetite helps weight loss.
Would this approach work for everybody? No, I'm sure their metabolism will adjust as you say. Will it help people morbidly obese eat less? It very well could. As such, I think it's a great discovery. I lost over 20 kgs the old fashioned way (more exercise and fewer calories eaten), and while that is the best (read healthiest) way to do it, not everybody has the willpower. I know if this gum were affordable, I would love a piece after dinner settles some days, because I probably eat 500+ calories a day snacking.
isnt reducing hunger in the majority of cases the solution?
Reply | Report Abuse | Link to thisAll OVERWEIGHT ISSUES are causes by stubborn insulin (Pets included)
Reply | Report Abuse | Link to this1. If you cannot lose weight it is caused by stubborn insulin (regardless of if you have diabetes)
2. Diets like Weight Watchers do not reverse stubborn insulin
3. When researchers used a Specialized diabetes diet in Holland people reverse stubborn insulin and received a normal blood sugar level.
4. The food chemicals allowed by the FDA has reated the crisis of obesity not McDonald's 4.6 million died this year from Diabetes http://spirithappy.org/wp/2011/09/14/diabetes-now-kills-4-6-million-every-year-diabetic-overweight-or-thin-the-illness-is-taking-lives/
Are we still going to blame McDonald's?
A worldwide famine is expected. The obese might be lucky some day.
Reply | Report Abuse | Link to thisVitamine B12 is known for helping normal functioning of the brain - maybe it helps as well to control the 'urge' to eat?
Reply | Report Abuse | Link to thisAs a young adult I lost nearly 25% of my body weight (read adipose tissue) through intensive exercise. However being the anal type, I was able to 'force' myself to endure this regime for several years. I now enjoy regular exercise (and eat a healthy diet) and have remained fit (and slim) well into my fifties.
Reply | Report Abuse | Link to thisHowever this regime, I am certain, would not work for the 'average' obese individual. We need to get back to the basics i.e. EDUCATION: eat a healthy diet, perform at least a moderate amount of physical activity.
Satiety control or some other artificial/medical intervention may be of use for the morbidly obese (or to 'kickstart' a health living change) but in general we need to move from this mindset of a 'quick fix' to trying to prevent the problem in the first instance.