Behind the shimmering prospect of a newly approved prescription weight-loss medication and the possibility of two more to come is a more distant glimmer of hope for those who have already cracked the obesity barrier: a vaccine that could reset the body's metabolism and prompt weight loss even with a modest change in calories taken in or burned up in exercise. New research on mice demonstrates it could happen.
The study tried two different formulations of a vaccine designed to reduce production of the hormone somatostatin in mice that had become obese after they were routinely fed high-fat chow. The formulations differed not in their bioengineered active ingredient but in the "adjuvant" that was added to stoke the body's response to the vaccine. Both formulations showed a marked effect: Compared with obese mice who did not get the vaccine, the weight gain of those who got either formulation slowed -- even though all the mice continued to get the same high-fat diet.
By the end of the study, the weight gain of vaccine-treated mice was a much smaller proportion of overall body weight than it was for those that got a sham infusion. And compared with the control group, the mice that got either vaccine formulation had notably higher levels of a hormone called "growth factor" (better known to humans as human growth factor, or HGH) and more modest increases in insulin-like growth factor 1 or IGF-1.
The study was published Monday in the Journal of Animal Science and Biotechnology, an open-access publication of BioMedCentral.
A vaccine that targets the hormone somatostatin builds on research that has been promising but highly controversial: a group of findings that set off a bull market for companies marketing the anabolic steroid synthetic Human Growth Factor and a stampede of steroid use by athletes and bodybuilders. Those trends exploded after a 1990 study in the New England Journal of Medicine found that injections of synthetic HGH increased muscle mass and decreased body fat in humans without changes in diet or exercise.
Somatostatin, which is normally produced in the brain's hypothalamus and in certain parts of the digestive system, inhibits the release of growth factor from the pituitary gland. So decreasing production of somatostatin would allow GF to build to higher levels -- in principle, like turning back the clock on metabolism to our teenage years, when HGH levels are naturally at their highest.
Since the 1990 study, subsequent research has found the effects of HGH to be more modest, but still notable: It has led to modest weight loss, reduced fat and increased muscle mass. In mice, it has led to reduced hypertension and improved cardiovascular function. But research has also revealed safety concerns: In adult humans who took the synthetic HGH, it increases risk of joint and muscle pain, insulin resistance, arm and leg swelling and carpal tunnel syndrome.
Marketing of synthetic HGH also increases the risk of getting ripped off: Unless injected, pills or powder forms will be broken down in the stomach and made useless; at about $1,000 a month, injectable forms of HGH -- which are given to children with growth deficiencies and adults with certain wasting diseases -- are a pretty expensive way to lose a little weight.
The American Assn. for Clinical Endocrinologists has warned that synthetic HGH should not be used to treat obesity in humans.
The current obesity vaccine effort rests on the hope that one could charge up the production of human growth hormone -- and the body's metabolism -- by manipulating the body's own hormonal chemistry that gives rise to its production. If it does, it might be used as a "prophylactic vaccine" -- used to prevent obesity in those prone to it -- or a therapeutic vaccine, used to treat or reverse an established condition.
Whether either will be safe, effective and cheap enough for use by millions of obese Americans will the subject of many future trials. The author of the current study -- Keith N. Haffer of Braasch Biotech in Garretson, S.D. --says that obese dogs and pigs could be next in line for testing with the experimental vaccine.