What do we know:
The hormone amylin is released from the pancreas after a meal and travels to parts of the brain, where it binds to amylin receptors, to tell you that you are full.
What don’t we know: Amylin receptors are expressed in many parts of the brain, but what are the specific brain regions in which amylin acts to affect how much you eat?
What this study shows: Amylin acts in a brain region called the lateral dorsal tegmental nucleus (LDTg) to tell you are full and decrease how much you eat.
What we can do in the future because of this study: We have identified an underappreciated brain region involved in hormonal control of feeding. This finding helps create a fuller picture of how hormones that are made in organs like the stomach, intestines, and pancreas affect how much you eat.
Why you should care: With over a third of the US population considered obese, it is very important to understand how our body and brain affect how much we eat. If we can understand how hormones act in the brain to make us feel hungry or full, we can potentially create new treatments for obesity.
The hormone amylin is released from the pancreas following a meal and has been traditionally thought to act exclusively in the hindbrain to decrease food intake. Recent findings have broadened the perspective of amylin's action in the brain to extend beyond the hindbrain to midbrain regions classically associated with reward. Here, the authors show that amylin acts in the lateral dorsal tegmental nucleus (LDTg), which connects the hindbrain and midbrain, to reduce food intake. The authors show that amylin in the LDTg decreases food intake by suppressing meal size without causing nausea. Knocking down amylin receptors in the LDTg increases food intake and body weight. Amylin receptor-expressing neurons in the LDTg make the inhibitory neurotransmitter GABA and blocking GABA receptors prevents the ability of amylin to decrease food intake. Together, these data demonstrate that amylin in the LDTg controls food intake.
The pancreatic-derived hormone amylin is classically thought to decrease food intake by activating neurons in the area postrema. Recent literature has shown that amylin can also act in the ventral tegmental area (VTA) to modulate the mesolimbic dopamine system and reduce food intake. The lateral dorsal tegmental nucleus (LDTg) sends reciprocal projections to the VTA as well as other nuclei important for feeding and reward and expresses receptors for many energy balance relevant signals. The LDTg may represent an understudied hub that potentially mediates energy balance. Here, the authors show that the LDTg expresses all the components of the amylin receptor and LDTg amylin receptor activation decreases food intake by suppressing meal size without producing nausea. LDTg amylin receptor knockdown increases food intake and body weight. Amylin receptor-expressing neurons in the LDTg are GABAergic and LDTg GABA receptor signaling is required for the hypophagic effects of LDTg amylin receptor. Together, these data suggest that amylin receptor signaling in the LDTg controls energy balance through GABA signaling.