Cover Story Current Issue

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges due to its hidden onset, high malignancy, and the lack of effective treatments. Together with surgery, adjuvant or neoadjuvant chemotherapy remains the primary treatment for patients with resectable or borderline resectable disease. However, the extensive metabolic reprogramming exhibited by pancreatic cancer cells interacts with oncogenes to affect the expression of key enzymes and signaling pathways, resulting in limited response to therapy and chemoresistance.

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Current Issue

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

Md Shahjalal H. Khan, Sora Q. Kim, Robert C. Ross, Florina Corpodean, ... Christopher D. Morrison

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

 

Objective

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences.

Methods and Results

In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. When the number of responses required to access protein reward varied, protein-restricted mice exhibited higher operant responses at moderate to high response requirements. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka). Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger dopamine neuron activation than casein in control diet-fed mice, while casein triggered a larger activation in low-protein diet-fed mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice.

Conclusion

These data suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

 

Articles in Press

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

Md Shahjalal H. Khan, Sora Q. Kim, Robert C. Ross, Florina Corpodean, ... Christopher D. Morrison

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling

 

Objective

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences.

Methods and Results

In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. When the number of responses required to access protein reward varied, protein-restricted mice exhibited higher operant responses at moderate to high response requirements. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka). Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger dopamine neuron activation than casein in control diet-fed mice, while casein triggered a larger activation in low-protein diet-fed mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice.

Conclusion

These data suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

 

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12th Helmholtz 
Diabetes Conference 

22-24. Sep, Munich

You are what you eat

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