Objective The objective of the current study was to compare the responses to different ex vivo immunogenic challenges between immune cells derived from metabolically healthy subjects with obesity and subjects with obesity and type 2 diabetes. Research design and methods We recruited 10 metabolically healthy subjects with obesity (Edmonton Obesity Staging System (EOSS) stage 0) and 9 subjects with obesity and type 2 diabetes (EOSS stage 2) aged between 21 years and 70 years and matched for body mass index. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell phenotypes and ex vivo cytokine production after phytohaemagglutinin (PHA, a T cell mitogen) stimulation were determined. Neutrophil oxidative burst activity was assessed in whole blood. Results PBMCs from subjects with stage 2 obesity produced significantly less interleukin (IL)-2, IL-6 and tumour necrosis factor α after PHA stimulation than PBMCs from subjects with stage 0 obesity (all, p<0.05). Subjects with stage 2 obesity also had higher proportions of cytotoxic T cells, activated helper T cells (CD4+CD278+) and inflammatory monocytes (CD14+CRTh2+, all p<0.05). Poststimulation, neutrophils from subjects with stage 2 obesity produced significantly more free radicals, were larger and more granular and had a lower stimulation index (all p<0.05). Conclusions Our results suggest that compared with obese individuals metabolically healthy individuals with obesity and type 2 diabetes have an impaired neutrophil function and T cell response on challenge despite having a T cell population expressing more activation markers which may be partly responsible for the increased prevalence of infection reported in this population.

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by social and communication deficits and repetitive behaviors. Children with ASD are also at a higher risk for developing overweight or obesity than children with typical development (TD). Childhood obesity has been associated with adverse health outcomes, including insulin resistance, diabetes, heart disease, and certain cancers. Importantly some key factors that play a mediating role in these higher rates of obesity include lifestyle factors and biological influences, as well as secondary comorbidities and medications. This review summarizes current knowledge about behavioral and lifestyle factors that could contribute to unhealthy weight gain in children with ASD, as well as the current state of knowledge of emerging risk factors such as the possible influence of sleep problems, the gut microbiome, endocrine influences and maternal metabolic disorders. We also discuss some of the clinical implications of these risk factors and areas for future research.

The prevalence of chronic kidney disease (CKD) is increasing and dietary interventions may be a strategy to reduce this burden. In the general population, higher potassium intake is considered protective for cardiovascular health. Due to the risk of hyperkalemia in CKD, limiting potassium intake is often recommended. However, given that poor cardiovascular function can cause kidney damage, following a low-potassium diet may be deleterious for patients with CKD. The aim of this systematic review was to summarize the evidence on dietary potassium intake and CKD progression. Multiple databases were searched on 7 June 2019 and data were managed with Covidence. No intervention trials met the inclusion criteria. Eleven observational studies met the inclusion criteria (10 post hoc analyses, 1 retrospective cohort), representing 49,573 stage 1-5 predialysis patients with CKD from 41 different countries. Of the 11 studies, 6 studies reported exclusively on early CKD (stage 1-2), 4 studies separately reported analyses on both early and late (stage 3-5) CKD, and 2 studies reported exclusively on late CKD. A total of 9 studies reported risk of disease progression in early CKD; in 4 studies high potassium intake was associated with lower risk, while in 2 studies the low intake showed a higher progression of risk, and 3 studies reported no relation. In late CKD, results are mixed: 2 studies suggested benefit of higher potassium intake and 1 suggested benefit of lower potassium intake, whereas 3 studies were neutral. These results should be interpreted with caution, as considerations preventing firm conclusions include 1) the overall low range of dietary potassium intake, with all studies reporting an average intake below the 2004 Kidney Disease Outcomes Quality Initiatives guidelines, and 2) the method used to assess potassium intake in most studies (i.e., urine) in late stages of CKD. Ideally, well-controlled intervention studies are needed to understand how dietary potassium intake is linked to CKD progression.

Patients with ulcerative colitis have low concentrations of the major membrane lipid phosphatidylcholine (PC) in gastrointestinal mucus, suggesting that defects in colonic PC metabolism might be involved in the development of colitis. To determine the precise role that PC plays in colonic barrier function, we examined mice with intestinal epithelial cell (IEC)-specific deletion of the rate-limiting enzyme in the major pathway for PC synthesis, CTP:phosphocholine cytidylyltransferase-α (CTαIKO mice). Colonic tissue of CTαIKO mice and control mice was analyzed by histology, immunofluorescence, electron microscopy, quantitative polymerase chain reaction, western blotting and thin-layer chromatography. Histopathological colitis scores were assigned by a pathologist blinded to the experimental groupings. Intestinal permeability was assessed by fluorescein isothiocyanate-dextran gavage and fecal microbial composition was analyzed by sequencing 16s ribosomal RNA amplicons. Subsets of CTαIKO mice and control mice were treated with dietary PC supplementation, antibiotics, or 4-phenylbutyrate. Inducible loss of CTα in the intestinal epithelium reduced colonic PC concentrations and resulted in rapid and spontaneous colitis with 100% penetrance in adult mice. Colitis development in CTαIKO mice was traced to a severe and unresolving endoplasmic reticulum (ER) stress response in IECs with altered membrane phospholipid composition. This ER stress response was linked to the necroptotic death of IECs, leading to excessive loss of goblet cells, formation of a thin mucus barrier, elevated intestinal permeability, and infiltration of the epithelium by microbes. Maintaining the PC content of IEC membranes protects against colitis development in mice, demonstrating a crucial role for IEC phospholipid composition in colonic homeostasis.

Obesity has emerged as a leading global health concern. It is characterized by chronic low-grade inflammation, which impairs insulin signaling, lipid metabolism and immune function. Recent findings from animal and clinical studies have begun to elucidate the underlying mechanisms of immune dysfunction seen in the context of obesity. Here, we provide a brief review on the current understanding of the interplay between obesity, dyslipidemia and immunity. We also emphasize the advantages and shortcomings of numerous applicable research models including rodents and large animal swine that aim at unraveling the molecular basis of disease and clinical manifestations. Although there is no perfect model to answer all questions at once, they are often used to complement each other. Finally, we highlight some emerging nutritional strategies to improve immune function in the context of obesity with a particular focus on choline and foods that contains high amounts of choline.