How are the arcuate nucleus feeding circuits and associated brainstem pathways characteristically altered under the influence of cancer-released inflammatory cytokines in a cachectic state?

Question

Accepted Answer

Arcuate nucleus circuits shift toward energy expenditure, exhibiting increased POMC activation and decreased AgRP/NPY tone, while tumour-derived GDF15 acts on brainstem GFRAL neurons.

Answer

Cytokines act on the arcuate nucleus to selectively upregulate AgRP/NPY tone, but this is rendered ineffective because MC4R receptors are blocked by circulating glucocorticoids.

Answer

The hypothalamic melanocortin system is completely shut down, causing NAc projection circuits to upregulate NPY tone, while brainstem GFRAL pathways are inhibited.

Answer

Circulating cytokines block the IL-1R to suppress POMC activation, while tumour-derived GDF15 selectively activates CGRP neurons in the brainstem to induce food-seeking behaviour.

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How are the arcuate nucleus feeding circuits and associated brainstem pathways c...

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