overactivated LH orexinergic (Orexin) terminals in the mPFC induced anhedonia but not anxiety and despair behaviors

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Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair (orexin)​

overactivated LH orexinergic terminals in the mPFC induced anhedonia but not anxiety and despair behaviors in naive mice. Moreover, chemogenetically inhibited LH–mPFC orexinergic projection neurons and blocked the orexin receptors in the mPFC alleviated anhedonia but not anxiety and despair behaviors in UCMS-treated mice. We found that the orexinergic neurons in the LH predominantly project to the glutamatergic neurons in the mPFC, and the excitability of these neurons were increased after UCMS unpredictable mild chronic stress. Our study identified a new neurocircuit from LH orexinergic neurons to mPFC and revealed its role in regulating anhedonia in response to stress.

https://www.nature.com/articles/s41398-024-02860-9

Fiber, especially fermentable fiber like resistant starch is turned into butyrate in our guts and activates GLP-1, which is a hormone that activates Orexin in the LH when it reaches the brain. Animal studies suggest that GLP-1 actually functions much like Orexin as well. https://pubmed.ncbi.nlm.nih.gov/15371515/

https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(20)30252-6

Other interactions of GLP-1 and glucose with Orexin https://forums.phoenixrising.me/thr...nfa-itaconate-shunt-part-2.89388/post-2437548

Note orexin has interaction also with er stress and therefore wasf3 levels, glucose and fructose have interaction with wasf3 levels as well.