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| Source: Wikipedia. Butter (fat) melting away... |
What if you could take a pill that would simply melt your fat away? The dream has become reality, but you have to be a chubby monkey to get your hands on it.
Barnhart and colleagues performed a placebo-controlled trial on adipotide, an experimental new drug to combat obesity, in obese rhesus monkeys. Adipotide acts to slowly destroy the blood vessels that feed fat tissue. By starving fat cells nutrients and oxygen, the cells eventually die, and fat loss ensues. The compound has shown considerable success in rodents, but in order for the drug to progress into human trials, the experiments had to be replicated in non-human primates. Indeed, the results are promising.
Spontaneously obese monkeys were given daily injections of adipotide, or placebo, for 28 days, followed by a 28 day recovery period. The treatment group enjoyed a 15% weight loss, on average, by the end of the eight weeks – equivalent to a 275 pound person losing 40 pounds. The bulk of the fat loss was visceral fat, which is the most deleterious region to carry body fat.
There is still plenty of time until it could be use to treat human obesity, but until then, the drug’s actions on fat tissue are interesting to ponder.
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| Souce: Wikipedia. Adipose (fat) tissue. The yellow fat cells are usually supplied by the red blood vessels. |
Adipotide is a protein-based compound that binds to the endothelial cells that line the vasculature of fat tissue. The protein enters the cells and causes them to commit planned suicide, or “apoptosis” in biology-speak. Deprived of blood, the fat cells progressively die-off as they starve of oxygen and nutrients. The fatty acids and triglycerides within the cells are released into the circulation and the body cleans-up the debris, leaving the monkeys svelte. But where does the fat go?
One would expect a flood of triglycerides into the blood stream. This is called hypertriglyceridemia and is a component of the metabolic syndrome and is a risk factor for heart disease. However, this doesn’t appear to be the case. The animals’ blood lipids improved throughout their weight loss. What’s more, the animals became considerably more insulin sensitive – an important improvement that prevents diabetes and other complications of obesity. Together, these data suggest that the freed fat was successfully oxidized, or “burned”, by the body for energy.
Throughout the treatment period, the monkeys receiving adipotide consumed fewer “biscuits” than their overweight controls. The authors attribute the poor appetite to enhanced satiety, rather than nausea, which in turn led to weight loss.
However, adipotide did not cause lean monkeys to eat less. The selective effect on appetite suggests that eating less isn’t the primary effect. And after all, the drug targets the fat cells, not the brain. Rather, it seems plausible that the dying fat cells free up an abundance of fat to be used for fuel. With plenty of fuel available to the body, there’s little reason to stock up on biscuits.
There isn’t any data measuring the type of fuel – carbohydrate or fat – metabolized by the monkeys, so the mechanism requires a bit of speculation.
The monkeys lose fat mass into the circulation, which gets oxidized for energy. Fat loss improves insulin sensitivity, so the animals don’t have to secrete as much insulin in order to compensate for insulin resistance. Plenty of fat for energy in the presence of lower insulin – remember, insulin drives fat storage – allows the monkeys to get by with eating less. It’s like a drug-induced low carb diet, but instead of a bun-less cheeseburger, the monkeys are able to dine on their fat stores. Although the cheeseburger would have one less side effect.
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| Source: Wikipedia. A lean (and wild) rhesus macaque |
The experimental monkeys showed transient problems with their kidneys, as indicated by elevated creatnine levels and slight microscopic damage to the tissue. It’s unclear from this study whether the problem stems from the drug itself or a complication from the dying fat cells. Side effects are especially problematic if adipotide needs to be taken chronically.
The monkeys started to show some regain of weight by the end of the four week recovery period, but the amount was minimal. This could be an inherent problem to the drug, or it could be because they stuck to their low-fat junk food diet - monkey chow composed of 59% carbohydrate, 28% protein, and 12% fat – that made them fat in the first place.
