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.