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The pancreas is a mixed gland primarily composed of exocrine tissue, which secretes digestive enzymes into the digestive tract, and an endocrine component organized into small clusters known as islets of Langerhans, constituting approximately 1% of the pancreatic mass. Each adult islet contains an average of 1,500 cells, including beta-, alpha- and delta-cells, which produce and secrete insulin (INS), glucagon (GCG), and somatostatin (SST) respectively. The destruction of insulin-producing beta-cells or the defective insulin secretion give rise to type 1 and type 2 diabetes mellitus, respectively. These chronic metabolic disorders are characterized by the dysregulation of glucose homeostasis. 

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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.

 

2022 impact factor: 6.6

You are what you eat

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