The FDA recently approved a new drug called lorcaserin (brand name Belviq) for the treatment of obesity. Lorcaserin causes an average of 13 lbs (5.8 kg) of weight loss over a year, compared to 5 lbs (2.2 kg) for placebo (1), which is less than the other recently approved drug Qsymia (formerly Qnexa; topiramate/phentermine).
Learning about obesity drugs is always a good opportunity to gain insight into the mechanisms that underlie the development and reversal of obesity. If you've been following this blog for a while, you already have a pretty good guess what organ this new drug acts on. Make your guess and read on!
Lorcaserin acts in the brain, like most other obesity drugs. In fact, I would say this drug is one of the most straightforward of all of them. It stimulates a specific neurotransmitter receptor, the serotonin 2C receptor, which is expressed in several brain regions. In particular, this receptor is expressed in the hypothalamus, in a key population of cells called POMC neurons. The hypothalamus is the central regulator of body fatness, and POMC neurons suppress food intake and lower fat mass when activated (2). POMC neurons express serotonin 2C receptors, and activating them with
serotonin, lorcaserin, or other drugs suppresses food intake and causes
fat loss. Research in mice has shown that POMC neuron signaling is required for the effects of similar drugs, suggesting that they act through this pathway (3, 4).
POMC neurons are an important part of the system that regulates body fatness in humans, but there are a number of other neuron populations that are also important (including the recently characterized NOS1 neurons, which seem to be very important; 5). Under normal circumstances, POMC neurons respond to circulating leptin, ghrelin, fatty acids, and other indicators of body energy status, using these signals to balance food intake, energy expenditure and fat storage. Lorcaserin bypasses this and stimulates POMC neurons directly, lowering food intake and the body fat "setpoint". It is truly amazing that stimulating a few hundred tiny neurons in the hypothalamus can have a significant effect on food intake and body fatness. These neurons all together could fit on the head of a pin.