The Penn group not only identified a necessary part of the brain which mediates the food intake suppression effect produced by these drugs, the nucleus tractus solitarius, or NTS, but also the cellular signaling pathways required for production of GLP-1's satiety effects.
"GLP-1's ability to alter these specific signaling pathways within the NTS of the brainstem may account for the suppression in food intake and body weight by altering the long-term neurochemistry and connectivity of this region of the brain with higher-order brain centers that also regulate energy balance," Bence said.
Many researchers have tried to determine precisely how GLP-1 and other satiating signals work, especially since in obese individuals, the brain fails to correctly perceive and respond to naturally occurring energy balance signals from the body. This faulty signaling underscores the importance of pharmacological treatments, such as the long-acting GLP-1 drugs that are effective in engaging brain signaling to reduce excessive food intake and possibly obesity.
That the Penn researchers were able to demonstrate a potential neurochemical mechanism of weight loss for a class of drugs already used in the treatment of type 2 diabetes provides a missing piece of the puzzle for future FDA-approved anti-obesity drugs.
"If we can identify other chemical signals or hormones that act on the same pathways that we've shown here, then by combined action you have a coordinated, orchestrated symphony of weight suppression," Hayes said.
|Contact: Evan Lerner|
University of Pennsylvania