The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review

Abstract

(1) Background: Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this systematic review, we focused on the potential roles of DNA methylation on mood disorders and obesity development. (2) Methods: This systematic review was conducted in accordance with the PRISMA statement and registered in Prospero. A systematic search was conducted in MEDLINE, Scopus, Web of Science, Cochrane Central database, EMBASE, and CINHAL. We also conducted a Grey literature search, such as Google Scholar. (3) Results: After deduplication, we identified 198 potentially related citations. Finally, ten unique studies met our inclusion criteria. We have found three overlap genes that show significant DNA methylation changes, both in obesity and depression. Pathway analysis interaction for TAPBP, BDNF, and SORBS2 confirmed the relation of these genes in both obesity and mood disorders. (4) Conclusions: While mechanisms linking both obesity and mood disorders to epigenetic response are still unknown, we have already known chronic inflammation induces a novel epigenetic program. As the results of gene enrichment, pathways analysis showed that TAPBP, BDNF, and SORBS2 linked together by inflammatory pathways. Hypermethylation in these genes might play a crucial rule in the co-occurrence of obesity and mood disorders.

SAM homeostasis is regulated by CFIm-mediated splicing of MAT2A

“…Therefore, SAM must be constantly produced to maintain SAM-to-SAH ratios sufficient to support methyltransferase activity ( Clarke, 2006 ; Krijt et al, 2009 ; Walsh et al, 2018 ). Too much or too little methylation of substrates by SAM has been associated with cancer, diabetes, along with other diseases ( Gharipour et al, 2020 ; McMahon et al, 2017 ; Zhu et al, 2020 ). Therefore, intracellular SAM levels are tightly controlled to maintain homeostasis, with loss of regulation resulting in cellular dysfunction ( Gao et al, 2019 ; Lio and Huang, 2020 ; Ouyang et al, 2020 ; Parkhitko et al, 2019 ).…”

Dietary Glutamic Acid, Obesity, and Depressive Symptoms in Patients With Schizophrenia

“…Additionally, these effects in animals have been found to be reversed by 7,8-dihydroxyflavone, a brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) agonist, which mechanistically may reverse glucocorticoid receptor phosphorylation (44). This finding in particular is important to this investigation, as BDNF hypermethylation has been previously reported as a link between obesity and depression in addition to its role in schizophrenia pathophysiology (10,12,45). Taken together then, these data suggest that the both the metabolic and behavioral effects of MSG may occur through epigenomic modulation potentially impairing the hypothalamic-pituitary-axis (HPA) feedback inhibition.…”

“…In addition to glutamate neurotransmission, epigenomic relationships between obesity, cardiovascular disease, psychosis, and depressive symptoms have been reported (10). In particular, hypermethylation of genes common to known obesity and depression pathways [i.e., Brain Derived Neurotropic Factor (BDNF)] may trigger various inflammatory cascades, which link diet, obesity, and depressive symptoms (10)(11)(12). This work also supports findings reported by our group examining gene specific methylation differences between schizophrenia and cardiovascular risk factors (13)(14)(15).…”

Identification of transcriptome alterations in the prefrontal cortex, hippocampus, amygdala and hippocampus of suicide victims

“…Indeed, abnormal levels of several amino acids have been recently identified in the peripheral blood of MDD patients 56 . Notch signaling is important in regulating neural cell proliferation, differentiation, and neural cellular growth, and is considered as a contributor in adaptive and innate immune responses and alterations in Notch signaling have been reported in mood disorders 57 .…”