Unraveling the connection between eosinophils and obesity

Calco, Gina N.; Fryer, A.D.; Nie, Zhenying

doi:10.1002/jlb.5mr0120-377r

Cited by 25 publications

(23 citation statements)

References 54 publications

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“…It has also been suggested that eosinophils may mediate glucose homeostasis and energy expenditure. However, the role of eosinophils in obesity is a matter of debate with studies showing conflicting findings, some suggesting that they protect from obesity while others suggest the opposite [113].…”

Section: Innate and Adaptive Immune Systemsmentioning

confidence: 99%

Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation

Bantulà

Roca‐Ferrer

Arismendi

et al. 2021

JCM

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Asthma and obesity are two epidemics affecting the developed world. The relationship between obesity and both asthma and severe asthma appears to be weight-dependent, causal, partly genetic, and probably bidirectional. There are two distinct phenotypes: 1. Allergic asthma in children with obesity, which worsens a pre-existing asthma, and 2. An often non allergic, late-onset asthma developing as a consequence of obesity. In obesity, infiltration of adipose tissue by macrophages M1, together with an increased expression of multiple mediators that amplify and propagate inflammation, is considered as the culprit of obesity-related inflammation. Adipose tissue is an important source of adipokines, such as pro-inflammatory leptin, produced in excess in obesity, and adiponectin with anti-inflammatory effects with reduced synthesis. The inflammatory process also involves the synthesis of pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and TGFβ, which also contribute to asthma pathogenesis. In contrast, asthma pro-inflammatory cytokines such as IL-4, IL-5, IL-13, and IL-33 contribute to maintain the lean state. The resulting regulatory effects of the immunomodulatory pathways underlying both diseases have been hypothesized to be one of the mechanisms by which obesity increases asthma risk and severity. Reduction of weight by diet, exercise, or bariatric surgery reduces inflammatory activity and improves asthma and lung function.

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Section: Innate and Adaptive Immune Systemsmentioning

confidence: 99%

Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation

Bantulà

Roca‐Ferrer

Arismendi

et al. 2021

JCM

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“…It is also worth mentioning that leptin promotes while adiponectin attenuates eotaxin-induced human eosinophil adhesion and chemotaxis (55, 218,219). Nevertheless, enhancing AT eosinophil abundance is debated since several studies demonstrated no beneficial or even negative outcomes of this approach (220). Required for the production of ROS LPS-treated mouse bone marrow-derived neutrophils treated with Antimycin A or myxothiazol (190) Required for migration Polg CRISPR/Cas9-mediated neutrophil-specific knockout in Zebra fish (191) Pentose phosphate pathway ⇑ Required for NETosis Amyloid fibril-and phorbol myristate acetate-stimulated human neutrophils (192) Required for ROS generation and NETosis G6PD-deficient patients G6PD-deficient mice (193,194) TCA cycle ⇑ Required for chemotaxis Isocitrate dehydrogenase 1 mutant mice (195) Required for differentiation Mouse Atg5-deficient neutrophils and an in vitro model of differentiating neutrophils (196) Lipogenesis ⇑ Required for differentiation Atg7-deficient neutrophil precursors (197) Required for neutrophil maintanence FASlox/lox-Rosa26-CreER mice (198) Glutamine metabolism It was suggested that circulating eosinophils display a greater metabolic flexibility in comparison to neutrophils (200,201).…”

Section: Eosinophilsmentioning

confidence: 99%

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

AlZaim

Hammoud

Al-Koussa

et al. 2020

Front. Cardiovasc. Med.

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Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation. Several lines of evidence link visceral and particularly perivascular, pericardial, and perirenal adipose tissue inflammation to the development of metabolic syndrome, insulin resistance, type 2 diabetes and cardiovascular diseases. In addition to the implication of the immune system in the regulation of adipose tissue function, adipose tissue immune components are pivotal in detrimental or otherwise favorable adipose tissue remodeling and thermogenesis. Adipose tissue resident and infiltrating immune cells undergo metabolic and morphological adaptation based on the systemic energy status and thus a better comprehension of the metabolic regulation of immune cells in adipose tissues is pivotal to address complications of chronic adipose tissue inflammation. In this review, we discuss the role of adipose innate and adaptive immune cells across various physiological and pathophysiological states that pertain to the development or progression of cardiovascular diseases associated with metabolic disorders. Understanding such mechanisms allows for the exploitation of the adipose tissue-immune system crosstalk, exploring how the adipose immune system might be targeted as a strategy to treat cardiovascular derangements associated with metabolic dysfunctions.

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“…It has been shown that, no matter the metabolic state displayed by the adipose micro-environment, both the homeostatic functions of eosinophils and the general mechanisms regulating eosinophil presence within adipose tissue are alike; including the mediation by a common tripod of type 2 innate lymphoid cells (ILC2s), IL-5, and eotaxin (4,5). However, the multiplicity of adipose micro-environmental factors potentially capable of establishing adipose eosinophilia and/or properly activate eosinophil functions is far more abundant and obviously not restricted to these three key players, and as shown here, may involve leptin as an additional molecular modulator.…”

Section: Discussionmentioning

confidence: 99%

“…It seems definitive that eosinophilia is a hallmark of lean adipose niches and that eosinophils counteract the obesity related chronic inflammation ( 18 , 48 ). This knowledge is derived from a large body of data using C57BL/6 mouse experimental models of obesity which established the reduction of homeostatic eosinophils in adipose tissue undergoing metabolic syndrome ( 4 , 5 ). Nevertheless, Lee et al.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, recent groundbreaking studies had further widened the understanding of eosinophil functions from disease-related pro-inflammatory to homeostatic immunomodulatory roles ( 2 , 3 ). Eosinophils are now acknowledged as key regulators of adipose tissue homeostasis, with roles in control of thermogenic energy expenditure and resident macrophages modulation ( 4 , 5 ). Therefore, characterization of adipose tissue-related molecular factors capable of regulating eosinophil activity is of particular interest.…”

Section: Introductionmentioning

confidence: 99%

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Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

et al. 2020

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Eosinophils are key regulators of adipose tissue homeostasis, thus characterization of adipose tissue-related molecular factors capable of regulating eosinophil activity is of great interest. Leptin is known to directly activate eosinophils in vitro, but leptin ability of inducing in vivo eosinophilic inflammatory response remains elusive. Here, we show that leptin elicits eosinophil influx as well as its activation, characterized by increased lipid body biogenesis and LTC 4 synthesis. Such leptin-triggered eosinophilic inflammatory response was shown to be dependent on activation of the mTOR signaling pathway, since it was (i) inhibited by rapamycin pre-treatment and (ii) reduced in PI3K-deficient mice. Local infiltration of activated eosinophils within leptin-driven inflammatory site was preceded by increased levels of classical mast cell-derived molecules, including TNFa, CCL5 (RANTES), and PGD 2. Thus, mice were pre-treated with a mast cell degranulating agent compound 48/80 which was capable to impair leptin-induced PGD 2 release, as well as eosinophil recruitment and activation. In agreement with an indirect mast celldriven phenomenon, eosinophil accumulation induced by leptin was abolished in TNFR-1 deficient and also in HQL-79-pretreated mice, but not in mice pretreated with neutralizing antibodies against CCL5, indicating that both typical mast cell-driven signals TNFa and PGD 2 , but not CCL5, contribute to leptin-induced eosinophil influx. Distinctly, leptininduced eosinophil lipid body (lipid droplet) assembly and LTC 4 synthesis appears to depend on both PGD 2 and CCL5, since both HQL-79 and anti-CCL5 treatments were able to inhibit these eosinophil activation markers. Altogether, our data show that leptin triggers eosinophilic inflammation in vivo via an indirect mechanism dependent on activation of resident mast cell secretory activity and mediation by TNFa, CCL5, and specially PGD 2 .

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Unraveling the connection between eosinophils and obesity

Cited by 25 publications

References 54 publications

Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation

Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases

Leptin Elicits In Vivo Eosinophil Migration and Activation: Key Role of Mast Cell-Derived PGD2

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