👤 Francisco A Monsalve

Obesity and depression are two of the most prevalent diseases with increasing trends worldwide; it has been some time since the first epidemiological associations were first described. Currently, there is abundant evidence showing the physiology and the molecular aspects that intersect the biology of both ailments. This narrative review aims to synthesize current evidence on the epidemiology and shared pathophysiology of obesity and major depressive disorder, emphasizing convergent inflammatory, neuroendocrine, metabolic, genetic, and gut-brain mechanisms. We aggregate evidence for a bidirectional relationship mediated by: (1) chronic low-grade inflammation (elevated CRP, IL-6, TNF-α; microglial activation); (2) HPA axis dysregulation (hyper/corticosteronemia, impaired feedback, altered CRH/ACTH signaling); (3) metabolic and neurotrophic signaling deficits (insulin and leptin resistance, dysregulated adipokines such as leptin/adiponectin, impaired BDNF and synaptic plasticity); (4) lipid-derived neurotoxicity and mitochondrial stress (saturated fatty acids, ceramides, oxidative stress); and (5) gut-brain axis perturbations (microbiota dysbiosis, increased intestinal permeability, LPS-driven endotoxemia, altered short-chain fatty acids and tryptophan-kynurenine metabolism). We highlight how these convergent pathways promote neuroinflammation and mood dysregulation in individuals with obesity and summarize clinical consequences for screening, integrated management, and targeted interventions that modulate immune, neuroendocrine, metabolic, and microbial processes. Finally, we outline priorities for identifying shared biomarkers and advancing personalized strategies via multi-omics and systems medicine to improve prevention, diagnosis, and treatment. Show less

Familial chylomicronemia syndrome (FCS) is a rare monogenic disorder characterized by severe hypertriglyceridemia caused by pathogenic variants in genes involved in triglyceride metabolism. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of triglyceride-rich lipoproteins. We present 3 unrelated cases of FCS with a newly identified homozygous complex insertion-deletion variant in GPIHBP1, namely c.460₄₆₁delinsAAA, p.Ala154Lysfs*153. All 3 cases presented with severe hypertriglyceridemia, a high FCS clinical score, and significantly reduced lipoprotein lipase (LPL) activity (being 6.6 mUI the value corresponding to 20% of normal activity). These observations expand the spectrum of pathogenic GPIHBP1 variants in FCS. The identification of GPIHBP1 variant reinforces the causal link between GPIHBP1 mutations and LPL deficiency, as evidenced by diminished LPL activity, and further expands the genetic landscape of FCS. Show less

Recent studies have associated alterations of neuronal plasticity in specific brain areas with suicidal behavior. The Notch signaling pathway plays a relevant role in the control of stem cell maintenance, cell migration, and neuronal plasticity. In the present study, the gene expression of the four Notch receptors (NOTCH1-4), the five canonical ligands (DLL1, DLL3, DLL4, JAGGED1, and JAGGED2), the two non-canonical ligands (DLK1 and DLK2), and the transcription factors (HES1, HEY1, and HEY2) were measured in the dorsolateral prefrontal cortex (DLPFC) and amygdala (AMY) of suicide victims (S; n = 13 males, with no clinical psychiatric history and non-treated with anxiolytic or antidepressant drugs) and their corresponding controls (C; n = 13 males) by real-time PCR. The results revealed a reduction of NOTCH2 and NOTCH1, NOTCH3, and NOTCH4 gene expression in the DLPFC and AMY of S compared with C, respectively. DLL1 levels were increased in the DLPFC and decreased in the AMY, whereas DLL4, JAGGED1, and JAGGED2 were significantly decreased in the regions analyzed. DLK1 was reduced in the AMY, whereas no changes were observed in the DLPFC and in DLK2 expression levels in any of the regions analyzed. HES1 was significantly reduced in both brain regions from S, whereas there were no significant changes in HEY1 and HEY2. This study provides evidence suggesting that the Notch signaling pathway could be a potential key target in the treatment of suicidal behaviors. Show less