Eirini Vagena et al have identified a molecular pathway that reveals how obesity acts as a causative factor in the development of depression. The study found that dietary intake of saturated fats disrupted hypothalamic functions by suppressing cAMP/PKA signalling through activation of phosphodiesterase 4A (PDE4A). This then led to a subsequent increase in the concentration of free fatty acid receptor 1 (FFAR1). Researchers observed depression-related behaviours among mice fed with a high-fat diet (HFD) for 3 to 8 weeks. The consumption of HFD selectively induced accumulation of palmitic acid in the hypothalamus, causing suppression of 3,5-cyclic AMP/ protein kinase A signalling pathway. The findings suggest that inhibition of FFAR1 and/or an increase of cAMP signalling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.
Source: Translational Psychiatry 9, Article number: 141 (2019) 10 May 2019 https://www.nature.com/articles/s41398-019-0470-1