A new study has found, on a molecular level, what causes some brains not to respond to leptin, the hormone that indicates the body has enough fat stores.
The condition, leptin resistance, is thought to be a primary factor in obesity, but the mechanisms that block the brain from picking up the signal to stop eating hadn’t been fully unpacked. Health experts, scientists and doctors have known for a while that high-fat eating habits are associated with leptin resistance, but in exactly what way was unclear.
The researchers found mice fed on a high-fat diet produced an enzyme called MMP-2 that clipped the brain’s leptin receptors, keeping the hormone from reaching the hypothalamus, the part of the brain that regulates hunger. However, mice that the team genetically modified to not produce MMP-2 continued to have healthy, intact leptin receptors, even when fed a high-fat diet. These mice gained less weight.
All of this is interesting, if not particularly helpful to humans, except for this part: The scientists further found that when they blocked the enzyme MMP-2, the brain’s leptin receptors remained intact and able to convey the hormone to the hypothalamus in the usual way. This makes the team hopeful that they’ve hit on an avenue of research toward treating leptin resistance in humans by blocking the blocker – MMP2.
“We opened a new field of study for metabolic disease,” says Rafi Mazor, a research scientist in the department of bioengineering at the University of California San Diego. “We need to ask what other pathways, in addition to leptin and its receptors, undergo a similar destructive process and what the consequences might be.”
The researchers say the next step is to conduct a large-scale clinical trial to analyze whether MMP-2 inhibitors may help people lose weight. Researchers say their findings suggest in those suffering from early stage obesity, leptin receptors may be clipped, but their neural pathways might remain intact, offering the possibility of regenerating receptors.
“There is still a lot of work to do to better understand receptor cleaving and the loss of cell function while on a high-fat diet,” Mazor says.
