Influencia de grelina y leptina sobre alteraciones psiquiátricas en sujetos con obesidad

La obesidad (índice de masa corporal [IMC] > 30 kg/m2) se define como el exceso en la proporción del tejido adiposo; consecuencia de un ingreso calórico superior al gasto energético del individuo. Es considerada un problema inflamatorio, sistémico, crónico y recurrente que causa diversas complicaciones. Esta enfermedad se ha relacionado con diversos problemas metabólicos y fisiológicos ampliamente estudiados; además de psicopatológicos.La obesidad es un problema de salud pública en diversos países, principalmente en Norteamérica. Se ha observado que sujetos que presentan obesidad manifiestan numerosas alteraciones psiquiátricas, entre ellas: depresión, ansiedad y trastorno por atracón. Por ello, diversos estudios han llegado a la conclusión de que las hormonas gastrointestinales fungen un papel crucial en el establecimiento de conductas, siendo la orexigénica grelina y la anorexigénica leptina 2 de las hormonas con mayor participación activa. Dicha intervención se debe a que ambas hormonas presentan receptores en sistema nervioso central, primordialmente en áreas del sistema límbico, regulador crucial de conductas hedónicas. Por lo tanto, en la presente revisión bibliográfica describiremos el papel de la grelina y la leptina sobre la expresión de conductas psicopatológicas comunes en sujetos que padecen obesidad

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old