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Blunted Vagal Cocaine- and Amphetamine-Regulated Transcript Promotes Hyperphagia and Weight Gain
Shin J Lee1, Jean-Philippe Krieger2, Macarena Vergara3
1Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
Cell Reports
|February 13, 2020
Summary
Cocaine- and amphetamine-regulated transcript (CART) in vagal afferent neurons controls food intake. Disruptions in this signaling contribute to obesity, suggesting therapeutic potential.
Area of Science:
- Neuroscience
- Gastroenterology
- Obesity Research
Background:
- Vagal nerve signaling is crucial for controlling eating behavior by transmitting gut signals to the brain.
- Obesity is associated with disruptions in this vagally mediated gut-brain communication.
- The cocaine- and amphetamine-regulated transcript (CART) neuropeptide's role in this pathway is not fully understood.
Purpose of the Study:
- To investigate the role of CART neuropeptide synthesized in vagal afferent neurons (VANs) in regulating food intake and body weight.
- To examine how CART signaling in the nucleus tractus solitarii (NTS) affects feeding behavior in normal and obese conditions.
- To explore the therapeutic potential of restoring CART signaling in obesity.
Main Methods:
- Assessed CART neuropeptide synthesis in VANs in response to food consumption in rats.
- Administered CART into the NTS and blocked endogenous CART to evaluate effects on food intake.
- Utilized viral-mediated Cartpt knockdown in VANs to study its impact on weight gain and feeding patterns.
- Compared CART signaling efficacy in normal chow-fed rats versus rats fed a high-fat, high-sugar diet.
Main Results:
- CART is synthesized proportionally to food intake in VANs of chow-fed rats.
- CART injection into the NTS reduced food intake, while blocking CART increased it, requiring intact VANs.
- VAN Cartpt knockdown led to increased weight gain, daily food intake, larger meals, and faster ingestion.
- In obese rats, meal-induced CART synthesis in VANs was blunted, and CART antibody lost its effect, but NTS CART injection remained anorexigenic.
Conclusions:
- CART neuropeptide in VANs plays a significant role in regulating food intake and meal patterns.
- Disrupted CART signaling in VANs contributes to obesity, particularly in response to obesogenic diets.
- Restoring disrupted VAN CART signaling presents a potential therapeutic strategy for obesity.
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