Obese or Not Obese, peptides may be the answer

Hormone May Be Key to Long-Term Weight Loss By LINDA A. JOHNSON (May 22)

A hormone thought to boost appetite rises in the bloodstream after dieters lose lots of weight, possibly explaining why it's so hard to keep weight off long term - and offering a new target for a diet drug, researchers say.
Their small study of severely obese people found much higher levels of a recently discovered hormone made by stomach cells, ghrelin, in the blood after the patients had lost significant weight.
However, very little ghrelin was in the blood of several people who lost weight after gastric bypass surgery, an operation that sews shut 95 percent of the stomach and reroutes the flow of food.
Not only did ghrelin levels not go up, but in people who lost an enormous amount of weight, it went way down,'' said Dr. David E. Cummings, an endocrinologist who led the researchers at the University of Washington and the Veterans Affairs Puget Sound Health Care System.
Cummings and Dr. Mitchell S. Roslin, chief of obesity surgery at Lenox Hill Hospital in New York, say the abnormally low ghrelin levels after gastric bypass could help explain why it is more successful than dieting or operations that simply reduce stomach size.
Ghrelin is thought to be nature's way of making people fatten up when food is plentiful to increase survival during cycles of famine, a protective mechanism now harmful when plenty of high calorie food is available.
The researchers and other experts say the findings are circumstantial evidence of ghrelin's effects, and more research is needed.
The body has multiple backup systems for regulating body weight, probably including other hormones not yet discovered, said Dr. Stephen H. Schneider, director of diabetes services at UMDNJ-Robert Wood Johnson Medical School in New Brunswick, N.J. This is probably one of a number of substances which control appetite,'' and it's unclear how they interact, he said.
The study, reported in Thursday's edition of the New England Journal of Medicine, involved patients who had sharply reduced their weight and kept stable for three months. Five patients who had gastric bypass surgery dropped from an average of 435 pounds to 280 pounds, while 13 people on a supervised low-fat, liquid diet dropped from an average weight of 220 pounds to 182 pounds.
In the diet group, ghrelin levels were consistently about 50 percent higher after weight loss. Levels spiked before meals and plunged after, both before and after weight loss.
The bypass group had barely detectable ghrelin levels and on average had 72 percent less ghrelin than five dieters who ended up at about the same body mass index, a ratio of weight to height. The bypass patients also had 77 percent less ghrelin on average than a comparison group of 10 normal-weight people.
Some 75,000 to 100,000 severely obese Americans are expected to undergo some type of bariatric, or stomach-reducing, surgery this year. Gastric bypass is meant only for people at least 100 pounds overweight.
Ghrelin, discovered about two years ago, has a role in promoting growth, from making children taller to building bone density.
Injecting the hormone in rodents makes them eat right away, but ghrelin has not been proven to stimulate appetite in people. Still, several major pharmaceutical companies are trying to develop drugs to block the hormone, Cummings said. "A true cure for obesity would be the biggest moneymaker that any drug company's ever seen,'' he said. <

Measurement of circulating Ghrelin levels in fasting rat¹ and human obesity² by Phoenix's Ghrelin RIA Kit have been published in Nature and Diabetes.

Serum Ghrelin-ir in SD Rats: 1.26 ą 0.14 ng/ml and the fasting SD Rats: 2.86 ą 0.28 ng/ml (non-extracted)¹; Plasma Ghrelin-ir in lean Caucasians: 155 ą 25 fmol/ml and obese Caucasians: 106 ą 23 fmol/ml².

Extent and direction of ghrelin transport across the blood brain barrier is determined by its unique primary structure

Differential transport of mouse ghrelin, des-octanoyl mouse ghrelin, and human ghrelin across the blood-brain barrier in mice. Although octanoylated (bioactive) mouse ghrelin crosses the mouse BBB predominantly in the brain-to-blood direction, passage for des-octanoyl mouse ghrelin was observed only in the blood-to-brain direction. Human ghrelin, which differs from mouse ghrelin by two amino residues only, was transported in both directions in mice. The extent and direction in which the ghrelin can cross the BBB is therefore influenced by at least two features of its primary structure, its post-translationally added fatty acid side chain and its amino acid sequence.

William A. Banks, Matthias Tschöp, Sandra M. Robinson and Mark L. Heiman. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. Vol. 302, Issue 2, 822-827, August 2002

Ghrelin enables the stimulation of growth hormone release and control of energy balance.
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