Absence of COVID-19 associated mucormycosis in a tertiary intensive care unit in the Netherlands.

Mucormycosis is a severe complication in critically ill COVID-19 patients. Throughout the pandemic, a notable prevalence of mucormycosis has been observed in the Indian population, whereas lower occurrences have been reported in Europe. However, limited data exist regarding its prevalence in Europe, which is potentially underestimated due to the low sensitivity of bronchoalveolar lavage (BAL) cultures. We aimed to evaluate the prevalence of mucormycosis in a high-risk critically ill COVID-19 population in the Netherlands, and to evaluate the potential benefit of adding Mucor PCR to BAL as part of routine follow-up. In this study, we included 1035 critically ill COVID-19 patients admitted to either one of the two ICUs at AmsterdamUMC between March 2020 and May 2022; of these, 374 had undergone at least one bronchoscopy. Following the AmsterdamUMC protocols, bronchoscopies were conducted weekly until clinical improvement was achieved. We cultured BAL fluid for fungi and used PCR and galactomannan testing to detect Aspergillus spp. Additionally, we retrospectively performed qPCR targeting Mucorales DNA in the BAL of 89 deceased patients. All cultures were negative for Mucorales, whereas 42 (11%) cultures were positive for Aspergillus. Furthermore, qPCR targeting Mucorales was negative in all 89 deceased patients. This study showed that pulmonary mucormycosis was not present in critically ill COVID-19 patients in two tertiary care ICUs. These results indicate routine Mucorales qPCR screening is not clinically necessary in a high-standard-of-care tertiary ICU in a low-endemic area.

Exploring the role of endocrine factors in sensitive parenting in men.

Parental sensitivity has been studied extensively in parenting research. Recently, there has been increasing attention to endocrine factors that may be related to parental sensitivity, such as oxytocin, vasopressin, testosterone, and cortisol. Although hormones do not act in isolation, few studies integrated multiple hormones and examined their combined associations with parental sensitivity. The current study aimed to explore the hormonal correlates of paternal sensitivity by examining in 79 first-time fathers of young infants (2-4 months old) (1) the separate and combined associations of basal oxytocin, vasopressin, testosterone, and cortisol levels with sensitivity, and (2) the associations between paternal sensitivity and oxytocin, vasopressin, testosterone, and cortisol reactivity following father-infant interactions. We additionally explored whether interactions between the various basal hormone levels could predict paternal sensitivity. Saliva for the quantification of fathers' hormone levels was sampled before and after an interaction with their infant to determine basal levels and reactivity. Results revealed no significant associations between sensitivity and basal hormone levels or reactivity. However, results indicated that cortisol and testosterone interacted in their effects on paternal sensitive parenting. Namely, fathers with low basal cortisol levels showed more sensitivity with increasing T levels, but fathers with high cortisol levels were less sensitive with increasing T levels. However, it should be noted that the latter slope was not significantly different from zero. These findings suggest that variations in parental sensitivity might be better explained by interactions between hormones than by single hormone levels.

Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction.

OBJECTIVE: Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. METHODS: From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. RESULTS: Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. CONCLUSIONS: This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.

Is dopaminergic medication dose associated with self-reported bruxism in Parkinson's disease? A cross-sectional, questionnaire-based study.

OBJECTIVES: It is not clear whether dopaminergic medication influences bruxism behaviour in patients with Parkinson's disease (PD). Therefore, the aims are to investigate (i) the prevalence of possible (i.e., self-reported) bruxism (sleep and awake) in PD patients, and (ii) whether the use of dopaminergic medication and other factors (viz., demographic characteristics, PD-related factors, and possible consequences of bruxism) are associated with possible bruxism (sleep or awake). MATERIALS AND METHODS: This study concerns a secondary analysis of an earlier published study. Three hundred ninety-five PD patients (67.9 ± 8.6 years of age; 58.7% males) were included. The levodopa equivalent daily dosage (LEDD) was used as a measure of the dopaminergic medication level. Subsequently, a logistic regression analysis was performed for the dependent variables 'awake bruxism' and 'sleep bruxism', with the following predictors: gender, age, LEDD, time since PD diagnosis, temporomandibular disorder (TMD) pain, jaw locks, and tooth wear. RESULTS: The prevalence of possible awake and sleep bruxism was 46.0% and 24.3%, respectively. Awake bruxism was associated with sleep bruxism (OR = 8.52; 95% CI 3.56-20.40), TMD pain (OR = 4.51; 95% CI 2.31-8.79), and tooth wear (OR = 1.87; 95% CI 1.02-3.43). Sleep bruxism was associated with tooth wear (OR = 12.49; 95% CI 4.97-31.38) and awake bruxism (OR = 9.48; 95% CI 4.24-21.19). Dopaminergic medication dose was not associated with awake bruxism (OR = 1.0; 95% CI 0.99-1.00) or sleep bruxism (OR = 1.0; 95% CI 0.99-1.00). CONCLUSION: Bruxism is a common condition in PD patients, but is not associated with the dopaminergic medication dose. CLINICAL RELEVANCE: (Oral) health care providers should be alerted about the possibility of sleep and awake bruxism activity in PD patients, along with this activity's possible negative health outcomes (viz., TMD pain, tooth wear).

Identification of dispersal barriers for a colonising seagrass using seascape genetic analysis.

Seagrasses are important habitats providing many ecological services. Most species have broad distributions with maximum dispersal distances of 100's of kms, however there is limited understanding of dispersal distances of colonising species like Halodule uninervis. It commonly grows in disturbed environments and could disperse to other meadows via clonal fragments. Effective conservation management requires greater understanding of genetic structure, dispersal barriers, and connectivity timescales to predict recovery following disturbance. Despite fragment viability of up to 28 days in a congenera, this theory remains untested in situ. Using 80 neutral single nucleotide polymorphisms, we investigated genetic diversity, gene flow patterns and structure among 15 populations of H. uninervis along 2000 km of Western Australian coastline. These data were combined with a multi-generational oceanographic dispersal model and a barrier dispersal analysis to identify dispersal barriers and determine which fragment dispersal duration (FDD) and timescale over which stepping-stone connectivity occurred, best matched the observed genetic structure. The 2-7 day FDD best matched the genetic structure with 4-12 clusters, with barriers to dispersal that persisted for up to 100 years. Modelling suggested greater fragmentation of metapopulations towards the southern edge of the species distribution, but genetic diversity did not decline. Several long-term boundaries were identified even with fragment viability of up to 28 days. This suggests H. uninervis dispersal is spatially limited by factors like oceanographic features and habitat continuity which may limit dispersal of this species. This study reiterates that potential dispersal does not equal realised dispersal, and management scales of 10's of kilometers are required to maintain existing meadows. Recruitment from distances further than this scale are unlikely to aid recovery after extreme disturbance events, particularly towards the range edge of H. uninervis distribution.

How the COVID-19 pandemic highlights the necessity of animal research.

Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future. This trend has led first and foremost to a substantial increase in the administrative burden and hurdles required to make timely advances in research and treatments for human and animal diseases. The current COVID-19 pandemic clearly highlights how much we actually rely on animal research. COVID-19 affects several organs and systems, and the various animal-free alternatives currently available do not come close to this complexity. In this Essay, we therefore argue that the use of animals is essential for the advancement of human and veterinary health.

Forensic validation of a SNP and INDEL panel for individualisation of timber from bigleaf maple (Acer macrophyllum Pursch).

Illegal logging is one of the largest illicit trades in the world, with high profits and generally low risks of detection and prosecution. Timber identification presents problems for law enforcement as traditionally used forensic methods such as wood anatomy and dendrochronology are often unable to confidently match wood evidence to the remains of illegally felled trees. Here we have developed and validated a set of genetic markers for individualisation in bigleaf maple (Acer macrophyllum), a high value timber species often felled illegally in the USA. Using 128 single nucleotide polymorphisms and three insertion/deletion markers developed through massively parallel sequencing, 394 individuals were genotyped on the MassARRAY® iPLEX™ platform (Agena Bio-science™, San Diego, USA) to produce a population reference database for the species. We demonstrate that the resulting DNA assay is reliable, species specific, effective at low DNA concentrations (<1 ng/µL) and suitable for application to timber samples. The PID for the most common profile, calculated using an overall dataset level FST-correction factor, was 1.785 × 10-25 and PID-SIB across all individuals (treated as a single population) was 2.496 × 10-22. The further development of forensic identification assays for timber species has the potential to deliver robust tools for improved detection and prosecution of illegal logging crimes as well as for the verification of legality in reputable supply chains.

The association of plasma fatty acids with hand and knee osteoarthritis: the NEO study.

OBJECTIVE: To investigate the association of postprandial and fasting plasma saturated fatty acid (SFAs), monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) concentrations with hand and knee osteoarthritis (OA). DESIGN: In the population-based NEO study clinical hand and knee OA were defined by the ACR classification criteria. Structural knee OA was defined on MRI. Hand and knee pain was determined by Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and KOOS, respectively. Plasma was sampled fasted and 150 min after a standardized meal, and subsequently analysed using a nuclear magnetic resonance platform. Logistic regression analyses were used to investigate the association of total fatty acid, SFA, MUFA, total PUFA, omega-3 PUFA and omega-6 PUFA concentrations with clinical hand and knee OA, structural knee OA and hand and knee pain. Fatty acid concentrations were standardized (mean 0, SD 1). Analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. RESULTS: Of the 5,328 participants (mean age 56 years, 58% women) 7% was classified with hand OA, 10% with knee OA and 4% with concurrent hand and knee OA. In men, postprandial SFAs (OR (95% CI)) 1.23 (1.00; 1.50), total PUFAs 1.26 (1.00; 1.58) and omega-3 PUFAs 1.24 (1.01; 1.52) were associated with hand OA. SFAs and PUFAs were associated with structural, but not clinical knee OA. Association of fasting fatty acid concentrations were weaker than postprandial concentrations. CONCLUSION: Plasma postprandial SFA and PUFA levels were positively associated with clinical hand and structural knee OA in men, but not in women.

The role of leptin and adiponectin as mediators in the relationship between adiposity and hand and knee osteoarthritis.

OBJECTIVES: To investigate associations of leptin and adiponectin levels with knee and hand osteoarthritis, and explore whether these mediate the association between adiposity and osteoarthritis. METHODS: This is a cross-sectional analysis of baseline data from the population-based Netherlands Epidemiology of Obesity study. Adiposity was assessed with body mass index (BMI) and percentage total body fat (%TBF). Osteoarthritis, defined as hand or knee osteoarthritis, was determined using American College of Rheumatology criteria. Fasting serum adipokine levels were measured using immunoassays. Associations between adiposity and osteoarthritis were examined with logistic regression, adjusted for age, sex, ethnicity and education, and additionally for leptin and adiponectin as potential mediators. RESULTS: In 6408 participants (56% women, median age 56 years), prevalence of osteoarthritis was 22% (10% isolated knee and 8% isolated hand osteoarthritis). Leptin levels were positively associated with osteoarthritis, while adiponectin levels were not. Leptin partially mediated the association of adiposity with osteoarthritis (OR 1.40 (95%CI 1.30; 1.52) attenuated to 1.38 (1.24; 1.54) per 5 units BMI and OR 1.25 (1.17; 1.35) to 1.20 (1.10; 1.32) per 5 units %TBF, representing 4% and 17% mediation, respectively). Larger proportion mediation by leptin was found in knee (13%/27%) than in hand osteoarthritis (9%/18%). Sex-stratified analyses generally showed stronger associations between adiposity, leptin and osteoarthritis in women than in men. CONCLUSIONS: Serum leptin levels were associated with osteoarthritis, and partially mediated the association between adiposity and osteoarthritis, while adiponectin levels were not associated with osteoarthritis. These findings provide evidence for systemic effects of adipose tissue in osteoarthritis.

[Early oral symptoms of Parkinson's disease]. / Vroege orale symptomen van de ziekte van Parkinson.

A family dentist established that the oral self-care of a 58-year-old man was suddenly inadequate. The dental hygienist who had been recruited subsequently noticed that the dexterity of the man was inadequate. The man's general medical practitioner referred him to a neurologist, who diagnosed Parkinson's disease. Due to this problematic situation, the man was off the family dentist's radar for approximately 1 year. Thereafter, a course of intensive support for his oral health behaviour was initiated. Given the progressivity of Parkinson's disease, it makes sense to aim at an oral health plan resistant to the patient's life course. The family dentist should be aware of his continuing responsibility to provide care and supervision until such time when informal and professional domiciliary care are no longer satisfactory or achievable and admission to a care facility is unavoidable. Only then can the family dentist hand over his responsibility to the geriatric dentist allied to that specific care facility.

The role of inflammation in the association between overall and visceral adiposity and subclinical atherosclerosis.

BACKGROUND AND AIMS: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis. METHODS AND RESULTS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) µm. Per SD of TBF (8%), cIMT was 19 µm larger (95% confidence interval, CI: 10, 28). This association was 17 µm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm2) VAT, cIMT was 9 µm larger (95% CI: 2, 16) which changed to 5 µm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers. CONCLUSION: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation.

[Possible treatment options for Parkinson's disease]. / Behandelingsmogelijkheden voor de ziekte van Parkinson.

Possible treatment options for Parkinson's disease consist of medications for motor symptoms as well as non-motor symptoms, such as cognitive decline, depression, hallucinations and delusions, constipation, and drooling. A number of these medications are in the experimental stage. In addition, physical activity and exercise can favourably influence the motor as well as the non-motor symptoms. Speech and dysphagia therapy are available, whereas cognitive behavioural therapy can control depressionand anxiety. Deep brain stimulation is the only surgical treatment currently used. Potential future surgical treatments are gene therapy, (stem) cell therapy, and the application of growth factors. Worldwide, research projects are being carried out in order to be able to control the disease. Once in a while surprising discoveries are made. Whether cure and/or prevention are possible remains to be seen.

Avoiding selection bias in metabolomics studies: a tutorial.

BACKGROUND: Metabolomics techniques are increasingly applied in epidemiologic research. Many available assays are still relatively expensive and therefore measurements are often performed in small patient population studies such as case series or case-control designs with strong participant selection criteria. Subsequently, metabolomics data are frequently used to assess secondary associations for which the original study was not explicitly designed. Especially in these secondary analyses, there is a risk that the original selection criteria and the conditioning that takes place due to this selection are not properly accounted for which can lead to selection bias. AIM OF REVIEW: In this tutorial, we start with a brief theoretical introduction on the issue of selection bias. Subsequently, we demonstrate how selection bias can occur in metabolomics studies by means of an investigation into associations of metabolites with total body fat in a nested case-control study that was originally designed to study effects of elevated fasting glucose. KEY SCIENTIFIC CONCEPTS OF REVIEW: We demonstrate that standard analytical methods, such as stratification or adjustment in regression analyses, are not suited to deal with selection bias and may even induce the bias when analysing metabolite-phenotype relationships in selected groups. Finally, we show that inverse probability weighting, also known as survey weighting, can be used in some situations to make unbiased estimates of the outcomes.

[Parkinson's disease: pathogenesis, aetiology, symptoms, diagnostics, and its course]. / Ziekte van Parkinson: pathogenese, etiologie, symptomen, diagnostiek en beloop.

Parkinson's disease is a slowly progressive neurodegenerative disorder characterised by motor symptoms, which are accompanied or often even preceded by non-motor symptoms. Pathologically, the disease is characterised by neural degeneration in specific brain regions, including the dopaminergic neurons of the pars compacta of the substantia nigra. At the molecular level, mitochondrial dysfunction, oxidative stress, altered protein handling, and reactive microgliosis contribute to the neural degeneration. Advanced age is a significant risk factor. Men are more often affected by the disease than women. Environmental, life-style and genetic factors are potential aetiological factors. The disease is primarily diagnosed on the basis of clinical features. In clinically uncertain cases, magnetic resonance imaging and dopamine transporter single-photon emission computer tomography can provide additional information. Patients usually die due to comorbidity. Parkinson's disease has also several negative influences on the orofacial system.

Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects.

BACKGROUND: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. METHODS: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. RESULTS: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). CONCLUSIONS: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.

A multicentre verification study of the QuantiFERON®-TB Gold Plus assay.

OBJECTIVES: The aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. RESULTS: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). CONCLUSION: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study.

INTRODUCTION: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. METHODS: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. RESULTS: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28-84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). CONCLUSION: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted.

IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcγ-receptor or complement.

BACKGROUND/OBJECTIVES: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. METHODS: We studied mice lacking all four FcγRs (FcγRI/II/III/IV-/-), only the inhibitory FcγRIIb (FcγRIIb-/-), only the central component of the complement system C3 (C3-/-), and mice lacking both FcγRs and C3 (FcγRI/II/III/IV/C3-/-). All mouse models and wild-type controls were fed a high-fat diet (HFD) for 15 weeks to induce obesity. Glucose metabolism was assessed and adipose tissue was characterized for inflammation and adipocyte functionality. RESULTS: In obese WAT of wild-type mice, B cells (+142%, P<0.01) and IgG (+128% P<0.01) were increased compared to lean WAT. Macrophages of FcγRI/II/III/IV-/-mice released lower levels of cytokines compared to wild-type mice upon IgG stimulation. Only C3-/- mice showed reduced HFD-induced weight gain as compared to controls (-18%, P<0.01). Surprisingly, FcγRI/II/III/IV-/- mice had deteriorated glucose tolerance (AUC +125%, P<0.001) despite reduced leukocyte number (-30%, P<0.05) in gonadal WAT (gWAT), whereas glucose tolerance and leukocytes within gWAT in the other models were unaffected compared to controls. Although IgG in gWAT was increased (+44 to +174%, P<0.05) in all mouse models lacking FcγRIIb, only FcγRI/II/III/IV/C3-/- mice exhibited appreciable alterations in immune cells in gWAT, for example, increased macrophages (+36%, P<0.001). CONCLUSIONS: Lack of FcγRs reduces the activity of macrophages upon IgG stimulation, but neither FcγR nor C3 deficiency protects against HFD-induced glucose intolerance or reduces adipose tissue inflammation. This indicates that if obesity-induced IgG contributes to the development of glucose intolerance, this is not mediated by FcγR or complement activation.