The molecular intricacies of hunger and satiety, pivotal for understanding metabolic disorders and the problem of obesity, are not yet fully understood by scientists. How much a person eats and weighs is regulated by a complex circuit regulated by the brain, and in order to understand it, researchers need to identify all the molecules involved. Now, a study from researchers at The Rockefeller University has identified an important a hormone responsible for regulating food intake, called amylin, which acts in the brain to help control consumption. The team state that their findings suggest that leptin and amylin work in concert to control food intake and body weight. The opensource study is published in the journal Cell Metabolism.
Earlier studies from the lab made the well-known discovery of the hormone leptin in 1994, one regulator in the consumption-control process. Defects in leptin production were shown to be associated with obesity. However, treating obesity with leptin alone has not proven effective except in cases of severe leptin deficiency, suggesting that additional components are involved in this system. Amylin caught the group’s attention when they were profiling a set of neurons in the hypothalamus, a part of the brain known to be involved in feeding behaviour. The current study explores amylin’s function in the brain, as it plays a role in sugar metabolism elsewhere in the body.
The current study identified the precursor to amylin, called Iselt amyloid peptide (Iapp), in the brain by using a technology known as translating ribosome affinity purification. Results show that Iapp is abundant in multiple regions throughout the hypothalamus. The researchers note that these findings contradict previous results which have not consistently found amylin, or Iapp, in the brain.
To tease out the function of amylin in the hypothalamus, the team assessed its presence in mice that were obese due to leptin deficiency. Data findings show that when these mice were given leptin, their Iapp levels increased significantly, indicating that leptin regulates the expression of amylin. The group also investigated how amylin and leptin affect feeding behaviour, with findings showing that when leptin was given to mice, it significantly suppressed food intake. In contrast, results show when leptin is given to mice whose amylin functional is inhibited, the effect of leptin is blunted. The lab state that this suggests leptin and amylin are working together in a way that reduces feeding.
Additionally, the researchers evaluated how amylin controls neural signals. From recordings of neuron signals showing that leptin and amylin act on the same neurons in similar ways, the group hypothesize that these hormones act in a synergistic manner, working together to produce an enhanced neural signal.
The team surmise that their findings confirm a functional role for amylin in the central nervous system, and provide a potential mechanism to treat obesity more effectively, through combination therapy. For the future, the researchers state that the global medical community still needs a better understanding of the cellular mechanisms involved in this system, which could provide new approaches that involve improved leptin signaling and sensitivity.
Source: The Rockefeller University
