Adipose Tissue Eosinophils Research Articles

Eosinophils prevent diet-induced airway hyperresponsiveness in mice on a high-fat diet.

Eosinophils contribute to metabolic homeostasis and airway hyperresponsiveness, but their specific role in obesity-related airway hyperresponsiveness remains unclear. To address this, we utilized transgenic mice that overexpress interleukin-5 (IL-5) in peripheral T cells (+IL-5T) and wild type controls. On a normal diet, +IL-5T and wild type mice have similar body weight, body fat, and airway nerve-mediated reflex bronchoconstriction in response to inhaled serotonin. Feeding wild type mice a 61.6% high-fat diet resulted in significantly increased body weight, body fat, fasting glucose, fasting insulin, and reflex bronchoconstriction induced by serotonin, which was blocked by vagotomy. In contrast, +IL-5T mice on a high-fat diet gained less body weight and fat than wild type mice on same diet and did not exhibit potentiation in fasting glucose, fasting insulin, or reflex bronchoconstriction induced by serotonin. Compared to wild type mice, +IL-5T mice on normal diet had significantly more adipose tissue eosinophils, and this was further increased by high-fat diet. High-fat diet did not increase adipose tissue eosinophils in wild type mice. Our findings suggest that adipose tissue eosinophils may play a role in regulating body fat, thereby reducing insulin, which is a mediator of obesity-related airway hyperresponsiveness. Thus, our data indicate adipose tissue eosinophils may be an important avenue for research in obesity-related asthma.

Obesity-related Asthma: A Pathobiology-based Overview of Existing and Emerging Treatment Approaches.

Though obesity-related asthma associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and glucagon-like-peptide 1 (GLP-1) receptor agonists, have been associated with improved asthma outcomes, though GLP-1R agonist data in asthma is limited to individuals with co-morbid obesity. Monoclonal antibodies approved for treatment of moderate to severe asthma generally appear to be effective in individuals with obesity, though this is based on retrospective or secondary analysis of clinical trials; moreover, while most of these asthma biologics are approved for use in the pediatric population, the impact of obesity on their efficacy has not been well studied in youth. Potential therapeutic targets being investigated include IL-6, arginine metabolites, nitro-fatty acids, and mitochondrial antioxidants, with clinical trials for each currently underway. Potential therapeutic targets include adipose tissue eosinophils and the GLP-1-Arginine-Advanced glycation end products axis, though data in humans is still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of interferon-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, in order to facilitate effective treatment development for this unique asthma phenotype.

The impact of eosinophilia on high fat diet-induced obesity and airway hyperresponsiveness

Hypothesis/Rationale: Eosinophils contribute to both adipose tissue metabolic homeostasis in obesity and airway hyperresponsiveness in asthma, but the role of eosinophils in obesity-related airway hyperresponsiveness is not understood. Considering that metabolic disorders increase the susceptibility to airway hyperresponsiveness in obese individuals, we investigated whether adipose eosinophils play a protective role in obesity-related airway hyperresponsiveness. Methods: Wild type (WT) and transgenic mice that overexpress interleukin 5 in peripheral T cells (+IL5T) were fed a high fat (61.6% fat) or normal chow (13.6% fat) diet for 19 weeks. Body weight, body fat, fasting glucose and insulin, and bronchoconstriction in response to inhaled serotonin were measured. The number of eosinophils were counted using flow cytometry in lung, adipose, and blood from transgenic WT and +IL5T mice with GFP-expressing eosinophils. Data: High fat diet significantly increased body weight and body fat in both WT and +IL5T mice, however +IL5T mice gained less weight and body fat than the WT mice. High fat diet increased fasting glucose, fasting insulin, and nerve-mediated airway responsiveness to inhaled serotonin in only the WT mice. On a normal chow diet, +IL5T mice had significantly more eosinophils in lung, blood, and adipose, and high fat diet further increased eosinophils in +IL5T adipose tissue. Acute administration of 1.29 U/kg (i.p.) insulin to a WT mouse on a normal chow diet significantly potentiated airway hyperresponsiveness to inhaled serotonin. Summary of results: Eosinophils in adipose tissue prevented high fat diet increases in circulating glucose and insulin, resulting in less body weight and body fat. This reduction in insulin by eosinophils in adipose tissue prevented obesity-related airway hyperresponsiveness. Conclusions: Insulin is a key modulator of obesity-related airway hyperresponsiveness. Eosinophils in adipose tissue play an important role in preventing obesity-related airway hyperresponsiveness by modulating insulin levels. Funding: NIH HL164474, NIH HL163087. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Linking adipose tissue eosinophils, IL-4, and leptin in human obesity and insulin resistance.

BACKGROUNDObesity is a multifactorial disease with adverse health implications including insulin resistance (IR). In patients with obesity, the presence of high circulating levels of leptin, deemed hyperleptinemia, is associated with IR. Recent data in mice with diet-induced obesity (DIO) show that a partial reduction in leptin levels improves IR. Additional animal studies demonstrate that IL-4 decreases leptin levels. In rodents, resident adipose tissue eosinophils (AT-EOS) are the main source of IL-4 and are instrumental in maintaining metabolic homeostasis. A marked reduction in AT-EOS content is observed in animal models of DIO. These observations have not been explored in humans.METHODSWe analyzed AT from individuals with obesity and age-matched lean counterparts for AT-EOS content, IL-4, circulating leptin levels, and measures of IR.RESULTSOur results show that individuals with obesity (n = 15) had a significant reduction in AT-EOS content (P < 0.01), decreased AT-IL-4 gene expression (P = 0.02), and decreased IL-4 plasma levels (P < 0.05) in addition to expected IR (P < 0.001) and hyperleptinemia (P < 0.01) compared with lean subjects (n = 15). AT-EOS content inversely correlated with BMI (P = 0.002) and IR (P = 0.005). Ex vivo AT explants and in vitro cell culture of primary human mature adipocytes exposed to either IL-4 or EOS conditioned media produced less leptin (P < 0.05).CONCLUSIONOur results suggest that IL-4 acts as a link between EOS, AT, and leptin production. Future studies exploring this interaction may identify an avenue for the treatment of obesity and its complications through amelioration of hyperleptinemia.TRIAL REGISTRATIONClinicaltrials.gov NCT02378077 & NCT04234295.

The regulatory role of eosinophils in adipose tissue depends on autophagy.

Obesity is a metabolic condition that elevates the risk of all-cause mortality. Brown and beige adipose tissues, known for their thermogenic properties, offer potential therapeutic targets for combating obesity. Recent reports highlight the role of immune cells, including eosinophils, in adipose tissue homeostasis, while the underlying mechanisms are poorly understood. To study the role of autophagy in eosinophils in this process, we used a genetic mouse model lacking autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage (Atg5 eoΔ). The absence of Atg5 in eosinophils led to increased body weight, impaired glucose metabolism, and alterations in the cellular architecture of adipose tissue. Our findings indicate that Atg5 modulates the functional activity of eosinophils within adipose tissue rather than their abundance. Moreover, RNA-seq analysis revealed upregulation of arginase 2 (Arg2) in Atg5-knockout eosinophils. Increased Arg2 activity was shown to suppress adipocyte beiging. Furthermore, we observed enrichment of the purine pathway in the absence of Atg5 in eosinophils, leading to a pro-inflammatory shift in macrophages and a further reduction in beiging. The data shed light on the importance of autophagy in eosinophils and its impact on adipose tissue homeostasis by suppressing Arg2 expression and limiting inflammation in adipose tissue.

Blood and adipose-resident eosinophils are defined by distinct transcriptional profiles.

Eosinophils are granular leukocytes of the innate immune system that play important functions in host defense. Inappropriate activation of eosinophils can occur in pathologies such as asthma and esophagitis. However, eosinophils also reside within adipose tissue, where they play homeostatic roles and are important in the activation of thermogenic beige fat. Here we performed bulk RNA sequencing in mouse adipose tissue-resident eosinophils isolated from both subcutaneous and gonadal depots, for the first time, and compared gene expression to blood eosinophils. We found a predominantly conserved transcriptional landscape in eosinophils between adipose depots that is distinct from blood eosinophils in circulation. Through exploration of differentially expressed transcription factors and transcription factors with binding sites enriched in adipose-resident eosinophil genes, we identified KLF, CEBP, and Fos/Jun family members that may drive functional specialization of eosinophils in adipose tissue. These findings increase our understanding of tissue-specific eosinophil heterogeneity, with implications for targeting eosinophil function to treat metabolic disorders such as obesity.

Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity.

BackgroundEpidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms Treg cells exert in the helminth-obesity interface has been poorly investigated. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity.Principal findingsThe presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by lower levels of leptin and resistin, lower infiltration of Th1 and Th17 cells in adipose tissue, higher expression of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also increase adipose Treg suppressor function in animals on high fat diet.ConclusionThese data suggest that H. polygyrus modulates adipose tissue Treg cells with implication for weight gain and metabolic syndrome.

76938 Does Decreased Adipose Tissue Eosinophil Content Impair Adipocyte Biology in Human Subjects with Obesity and Insulin Resistance?

ABSTRACT IMPACT: Extrapolating from mouse data we explored eosinophil content in human adipose tissue and its effect on adipocyte biology potentially leading to the discovery of novel therapeutic targets for treatment of obesity and insulin resistance. OBJECTIVES/GOALS: The interaction between immune cells and adipose tissue (AT) in obesity has not been fully elicited. Mouse models of diet-induced-obesity show AT resident eosinophils (EOS) help preserve insulin sensitivity (IS). As data in human obesity are lacking, here we explored AT-EOS content and their role in AT metabolism in subjects with and without obesity. METHODS/STUDY POPULATION: We recruited lean (L) subjects and patients with obesity (Ob) to undergo abdominal subcutaneous AT biopsy and evaluation of insulin resistance (IR) by determination of HOMA-IR. Circulating EOS were isolated from all participants under fasting conditions and exposed to high glucose (HG) or high lipids (HL) for 4 hrs. AT EOS number was assessed via FACS analysis. Circulating EOS and AT mRNA was assessed by qPCR for multiple genes involved in inflammation and cell migration. To evaluate the effect of EOS on primary human adipocytes, in vitro cultures were exposed for 4 days to either interleukin-4 (IL-4), interleukin-13 (IL-13) or to human EOS. Adipocytes mRNA levels were evaluated for genes involved in adipogenesis and lipid metabolism. RESULTS/ANTICIPATED RESULTS: 16 lean, IS subjects (BMI 22.5+ 0.4kg/m2) and 22 age-matched IR patients with obesity (BMI: 38.9 + 1.0kg/m2) participated. We observed a ratio of 2:1 in AT EOS content of L vs Ob subjects (P&lt;0.03). To assess the reduced AT-EOS content in obesity, we evaluated expression of Chemokine-C receptor 3 (CCR3) in circulating EOS. We show decreased CCR3 mRNA levels in Ob vs L subjects (P=0.006). We expect HL in vitro experiments on peripheral EOS of L subjects to affect CCR3 mRNA levels. In AT of Ob subjects, we found a significant decreased expression of Eotaxin 2, the main EOS chemokine binding CCR3 expressed on EOS. Preliminary data from in vitro primary adipocytes culture suggest for IL-4 and IL-13 to increase mRNA level of Peroxisome Proliferator Activated Receptor Gamma (PPARG), the master regulator of adipogenesis. DISCUSSION/SIGNIFICANCE OF FINDINGS: Comparable to animal studies, we found a decrease of AT-EOS content in patients with obesity. Alterations in CCR3/Eotaxin 2 signaling may be involved. IL-4 &amp;IL-13 are secreted predominantly by EOS and appear to directly regulate gene expression in human adipocytes. These data represent the first evidence for a novel role of EOS in human AT biology.

Can eosinophils in adipose tissue add fuel to the fire?

In inguinal adipose tissue, beige adipocytes are interspersed among white adipocytes and in close communication with dynamic populations of immune cells. Recent data have demonstrated that anti-inflammatory macrophages (M2) increase thermogenic activity of beige adipocytes, although the mechanism is currently under debate. ILC2, cells via secretion, of methionine enkephalin peptide were found to be able to increase beige thermogenesis. Knights et al. have recently generated a whole-body knock-out of KLF3 (KLF3-/-) to explore its contribution to thermogenesis and weight gain in a diet-induced obesity animal model.

Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age.

Adipose tissue eosinophils (ATEs) are important in the control of obesity-associated inflammation and metabolic disease. However, the way in which ageing impacts the regulatory role of ATEs remains unknown. Here, we show that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in both humans and mice. We find that exposure to a young systemic environment partially restores ATE distribution in aged parabionts and reduces adipose tissue inflammation. Approaches to restore ATE distribution using adoptive transfer of eosinophils from young mice into aged recipients proved sufficient to dampen age-related local and systemic low-grade inflammation. Importantly, restoration of a youthful systemic milieu by means of eosinophil transfers resulted in systemic rejuvenation of the aged host, manifesting in improved physical and immune fitness that was partially mediated by eosinophil-derived IL-4. Together, these findings support a critical function of adipose tissue as a source of pro-ageing factors and uncover a new role of eosinophils in promoting healthy ageing by sustaining adipose tissue homeostasis.

Eosinophil function in adipose tissue is regulated by Kr\xfcppel-like factor 3 (KLF3)

The conversion of white adipocytes to thermogenic beige adipocytes represents a potential mechanism to treat obesity and related metabolic disorders. However, the mechanisms involved in converting white to beige adipose tissue remain incompletely understood. Here we show profound beiging in a genetic mouse model lacking the transcriptional repressor Krüppel-like factor 3 (KLF3). Bone marrow transplants from these animals confer the beige phenotype on wild type recipients. Analysis of the cellular and molecular changes reveal an accumulation of eosinophils in adipose tissue. We examine the transcriptomic profile of adipose-resident eosinophils and posit that KLF3 regulates adipose tissue function via transcriptional control of secreted molecules linked to beiging. Furthermore, we provide evidence that eosinophils may directly act on adipocytes to drive beiging and highlight the critical role of these little-understood immune cells in thermogenesis.

Unraveling the connection between eosinophils and obesity

Obesity affects more than 650 million adults worldwide and is a major risk factor for a variety of serious comorbidities. The prevalence of obesity has tripled in the past forty years and continues to rise. Eosinophils have recently been implicated in providing a protective role against obesity. Decreasing eosinophils exacerbates weight gain and contributes to glucose intolerance in high fat diet-induced obese animals, while increasing eosinophils prevents high-fat diet-induced adipose tissue and body weight gain. Human studies, however, do not support a protective role for eosinophils in obesity. More recent animal studies have also reported conflicting results. Considering these contradictory findings, the relationship between eosinophils and obesity may not be unidirectional. In this mini-review, we summarize a recent debate regarding the role of adipose tissue eosinophils in metabolic disorders, and discuss local and systemic effects of eosinophils in obesity. Given that adipose eosinophils play a role in tissue homeostasis, more research is needed to understand the primary function of adipose tissue eosinophils in their microenvironment. Therapeutic interventions that target eosinophils in adipose tissue may have the potential to reduce inflammation and body fat, while improving metabolic dysfunction in obese patients.

2110-P: Increased Proinflammatory Eosinophils in Adipose Tissue of Metabolic Syndrome

Metabolic Syndrome (MetS) is a common disorder that predisposes to type 2 diabetes mellitus (T2DM) and cardiovascular disease (ASCVD). Adipose tissue (AT) contributes significantly to increased inflammation and insulin resistance (IR) in MetS. Many studies illustrate the role of macrophages and lymphocytes in human SAT, but there is sparse data on other immune cells, especially eosinophils. Hence, in this report we investigated the abundance of eosinophils (EOS) in subcutaneous AT (SAT) of 20 patients with MetS without diabetes, ASCVD, smoking or any inflammatory condition, and matched controls. SAT EOS were quantified by immunochemistry using the Vital New Red stain (ABCAM). Both circulating and SAT EOS were significantly increased 2-fold in MetS (p&amp;lt;0.007) and correlated with each other (r=0.40, p=0.03). Circulating EOS correlated significantly (p&amp;lt;0.05) with triglycerides (TG) (r=0.56), HDL-cholesterol (r=-0.45), IL-6 (r=0.57) and chemerin (r=0.61). SAT EOS correlated significantly (p&amp;lt;0.05) with cardio-metabolic factors including glucose (r=0.42), TG (r=0.39), and adipose IR(r=0.64), biomarkers of inflammation, including leptin (r=0.41), IL-6 (r=0.44), adiponectin (r=-0.39), endotoxin (r=0.56), and chemerin, (r=0.57), and SAT markers of fibrosis (collagen (r=0.42) and Sirius red (r=0.44)). In conclusion, we make the novel observation that eosinophils are increased in MetS and that SAT EOS are pro-inflammatory and promote fibrosis in SAT. Hence, they contribute to the dysregulation of SAT biology in MetS. Disclosure K. Moussa: None. P. Gurung: None. S. Devaraj: None. I. Jialal: None.

Increased eosinophils in adipose tissue of metabolic syndrome

AimsMetabolic Syndrome (MetS) is a common global disorder that predisposes to both Type 2 diabetes mellitus (T2DM) and cardiovascular disease (ASCVD). Adipose tissue (AT) contributes significantly to increased inflammation and insulin resistance (IR) in MetS which appear to be the crucial underpinnings of MetS. Compared to macrophages and lymphocytes in human subcutaneous AT (SAT), there is sparse data on the role of other immune cells, especially eosinophils (EOS). In this study, we investigated the abundance of EOS in the SAT of 19 patients with MetS without diabetes, ASCVD, smoking or any inflammatory condition, and matched controls. MethodsSAT EOS were quantified by immunohistochemistry. ResultsBoth circulating and SAT EOS were significantly increased 2-fold in MetS and correlated with each other. Circulating EOS correlated significantly with triglycerides (TG), high-sensitivity CRP, leptin, and IL-6. SAT EOS correlated significantly with plasma glucose, TG, FFA, adipose-IR, leptin, IL-6, endotoxin, chemerin and inversely with adiponectin. They also correlated with SAT markers of fibrosis: collagen and Sirius red staining of SAT. ConclusionWe make the novel and seminal observation that eosinophils are increased in SAT of MetS patients, and are associated with the pro-inflammatory state. Hence, in humans, they appear to contribute to the dysregulation of SAT biology in MetS.

Defining Eosinophil Function in Adiposity and Weight Loss.

Despite promising early work into the role of immune cells such as eosinophils in adipose tissue (AT) homeostasis, recent findings revealed that elevating the number of eosinophils in AT alone is insufficient for improving metabolic impairments in obese mice. Eosinophils are primarily recognized for their role in allergic immunity and defence against parasitic worms. They have also been detected in AT and appear to contribute to adipose homeostasis and drive energy expenditure, but the underlying mechanisms remain elusive. It has long been recognized that immune cells such as macrophages respond to external signals to regulate adipose homeostasis and energy balance, however, less is known about the relevance of eosinophil activity in AT. As the authors propose in this review, given recent debate over the relative importance of their tissue-specific abundance, the stage is now set for exploring the functionality and activation states of AT eosinophils.

A potential role for adipose tissue eosinophils in allergy and asthma.

Abstract Allergy can take many forms, but a mutual trait is the hypersensitive immune response to what the body detects as foreign. A common form of airway allergy is asthma, which affects &amp;gt;235 million people worldwide and is the most common chronic disease among children. Interestingly, obese individuals have a staggering 92% increased risk of asthma, displaying enhanced asthmatic symptoms, airway hyper-responsiveness, &amp; atopy. Due to the clinical correlation between obesity &amp; asthma, scientific endeavors have sought to explain the causality. Studies have shown adipokines secreted from adipose tissue (AT) can have either pro- or anti-inflammatory effects on the lungs. Furthermore, diet-induced obesity increases migration of eosinophils from bone marrow to the lung, as well as delays exit from the airway epithelium to the lumen. Curiously, investigators have tried to understand the correlative link between asthma &amp; obesity without closely examining the AT itself. Our data shows for the first time that AT mounts a hypereosinophilic state upon repeated exposure to a foreign substance (i.e. a hallmark of allergy &amp; asthma in lung); increasing eosinophils from ~5% to 60% of AT leukocytes in obese mice. A single exposure does not elicit an eosinophilic response, potentially suggesting a role for the adaptive immune system. We found that obesity increased sensitivity of this immune response. Furthermore, the surge in AT eosinophils was dependent on IL33, a required cytokine for eosinophilic accumulation in lung during allergy. We are determining if other classic indicators of allergy are present in AT of our model. Ultimately, we hope to elucidate whether AT &amp; lung act within a feedback loop that contributes to the incidence/severity of allergy &amp; asthma.

CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production

Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation of Il5Tg/Cd300f−/− mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Consequently, Il5Tg/Cd300f−/− mice had increased alternatively activated macrophage accumulation in the adipose tissue. Cd300f−/− mice displayed age-related accumulation of eosinophils and macrophages in the adipose tissue and decreased adipose tissue weight, which was associated with decreased diet-induced weight gain and insulin resistance. Notably, Il5Tg/CD300f−/− were protected from diet-induced weight gain and glucose intolerance. These findings highlight the cross-talk between IL-5 receptor and CD300f as a novel pathway regulating adipose tissue eosinophils and offer new entry points for therapeutic intervention for obesity and its complications.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes.

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function.

Mechanisms of human eosinophil migration induced by the combination of IL-5 and the endocannabinoid 2-arachidonoyl-glycerol

Mechanisms of human eosinophil migration induced by the combination of IL-5 and the endocannabinoid 2-arachidonoyl-glycerol