Depression and type 2 diabetes (T2D) are often seen together (Dutheil et al., 2016).

What are the mechanisms in psychoneuroimmunology (PNI) associated with these diseases? What are the roles of high-fat diets in anxiety and depression? How can the high-fat diets affect the brain and genetic signaling pathways?

Studies have indicated that having high-fat diets (HFD) for about 4 months may lead to anxiety and depressive problems (Dutheil et al., 2016). At the molecular level, high-fat diets may result in the dysfunctions in the intracellular networks associated with synaptic plasticity and insulin signaling. The changes also affect extracellular signal-regulated kinase (ERK) and P70S6K.

These alterations may affect the glucose homeostasis (Dutheil et al., 2016). In addition, higher corticosterone concentrations and abnormal innate immunity have been observed.

In addition, the higher levels of proinflammatory cytokines including IL-6, IL-1β, and TNFα may be induced (Dutheil et al., 2016). Moreover, drug interventions targeting the innate immunity and inflammation via the suppression of the purinergic P2X7 receptor have been found to ease the anxiety from HFD.

Studies have also observed that the antidepressant ketamine may relieve the anxiety problems from HFD (Dutheil et al., 2016). The drug may work on the ERK and P70S6 kinase signaling pathways in the brain regions including the prefrontal cortex.

Relevant studies have revealed the signaling pathways associated with chronic HFD that can lead to anxiety and depression (Dutheil et al., 2016). These networks can become the potential targets for the prevention and treatment of the comorbidity including anxiety, depression, and diabetes.

[Reference]

Dutheil S, Ota KT, Wohleb ES, Rasmussen K, Duman RS. High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation. Neuropsychopharmacology. 2016 Jun;41(7):1874-87. doi: 10.1038/npp.2015.357.

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