Researchers from the U.S. and the U.K. investigated whether obesity is a causative factor for the development of depression and the molecular pathways linked to these two disorders. Their results were published in the journal Translational Psychiatry.
- Obesity is associated with an increased risk of depression.
- To examine the relationship between these two, the researchers used lipidomic and transcriptomic methods to identify the mechanism that links a high-fat diet with alterations in hypothalamic function that lead to depression.
- They found that HFD selectively induces the accumulation of palmitic acid in the hypothalamus, suppresses the 3′,5′-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increases the concentration of free fatty acid receptor 1 (FFAR1).
- The researchers also found that a deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and controls stimulatory regulative G protein (Gs)-coupled receptor signaling, can protect from genetic- or dietary-induced depression.
Based on these findings, the researchers concluded that consumption of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling via activation of PDE4A. They also believe that FFAR1 inhibition and/or an increase in cAMP signaling is a potential therapeutic target that can counteract the effects of dietary or genetically induced obesity on depression.
Read the full article at this link.
Journal Reference:
Vagena E, Ryu JK, Baeza-Raja B, Walsh NM, Syme C, Day JP, Houslay MD, Baillie GS. A HIGH-FAT DIET PROMOTES DEPRESSION-LIKE BEHAVIOR IN MICE BY SUPPRESSING HYPOTHALAMIC PKA SIGNALING. Translational Psychiatry. 10 May 2019;9(1). DOI: 10.1038/s41398-019-0470-1
