Associations of TNFA, IL17A, and RORC mRNA expression levels in peripheral blood leukocytes with obesity-related asthma in adolescents.

Obesity is associated with a unique non-T2 asthma phenotype, characterised by a Th17 immune response. Retinoid-related orphan receptor C (RORC) is the master transcription factor for Th17 polarisation. We investigated the association of TNFA, IL17A, and RORC mRNA expression levels with the non-T2 phenotype. We conducted a cross-sectional study in adolescents, subdivided as follows: healthy (HA), allergic asthma without obesity (AA), obesity without asthma (OB), and non-allergic asthma with obesity (NAO). TNFA, IL17A, and RORC mRNA expression in peripheral blood leukocytes were assessed by RT-PCR. NAO exhibited higher TNFA mRNA expression levels than HA or OB, as well as the highest IL17A and RORC mRNA expression levels among the four groups. The best biomarker for discriminating non-allergic asthma among obese adolescents was RORC mRNA expression levels (area under the curve: 0.95). RORC mRNA expression levels were associated with the non-T2 asthma phenotype, hinting at a therapeutic target in obesity-related asthma.

IL-17A and TNF-α as potential biomarkers for acute respiratory distress syndrome and mortality in patients with obesity and COVID-19.

Coronavirus disease 2019 (COVID-19) was declared a pandemic and international health emergency by the World Health Organization. Patients with obesity with COVID-19 are 7 times more likely to need invasive mechanical ventilation than are patients without obesity (OR 7.36; 95% CI: 1.63-33.14, p = 0.021). Acute respiratory distress syndrome (ARDS) is one of the main causes of death related to COVID-19 and is triggered by a cytokine storm that damages the respiratory epithelium. Interleukins that cause the chronic low-grade inflammatory state of obesity, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant peptide (MCP)-1, and, in particular, IL-17A and tumour necrosis factor alpha (TNF-α), also play very important roles in lung damage in ARDS. Therefore, obesity is associated with an immune state favourable to a cytokine storm. Our hypothesis is that serum concentrations of TNF-α and IL-17A are more elevated in patients with obesity and COVID-19, and consequently, they have a greater probability of developing ARDS and death. The immunobiology of IL-17A and TNF-α opens a new fascinating field of research for COVID-19.

Decreased methylation profiles in the TNFA gene promoters in type 1 macrophages and in the IL17A and RORC gene promoters in Th17 lymphocytes have a causal association with non-atopic asthma caused by obesity: A hypothesis.

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.

Effect of supplementation with omega-3 fatty acids on hypertriglyceridemia in pediatric patients with obesity.

Background The beneficial effects of treating hypertriglyceridemic adults with omega-3 fatty acids have been reported. However, information regarding omega-3 treatment of pediatric patients is limited. To evaluate the efficacy and safety of administering omega-3 fatty acids (3 g/day for 12 weeks) to children/adolescents with obesity and hypertriglyceridemia. Methods A randomized, double-blind, placebo-controlled, parallel study involving pediatric patients (10-16 years old) with obesity and hypertriglyceridemia was conducted. The National Center for Health Statistics (CDC) defines obesity as a body mass index (BMI) ≥95th percentile. Subjects with triglyceride concentrations ranging from 150 to 1000 mg/dL were randomized into two groups: those receiving omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) (n = 65) and those receiving a placebo (n = 65) for 12 weeks. Serum triglyceride concentrations were always measured from 8 to 9 am after a 12-h fast. Results By the end of treatment, triglyceride concentrations had decreased by 39.1% in the omega-3 group and 14.6% in the placebo group (p < 0.01). The incidence of adverse gastrointestinal events (e.g. flatulence, belching) was 41.2% and 6.2% in the omega-3 and placebo groups, respectively (p < 0.01). There were no serious drug-related adverse events. Conclusions Supplementation with 3 g/day of omega-3 fatty acids is a safe and effective option for treating hypertriglyceridemia in children and adolescents with obesity.