Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis

By Davina Wu, Ari B. Molofsky, Hong-Erh Liang, R. Ricardo-Gonzalez, H. Jouihan, Jennifer K. Bando, A. Chawla, R. Locksley. Science, 2011

1,356 citations recorded by the source corpus.

Regulation of adipose tissue macrophages by eosinophils reveals an unexpected role for eosinophils in metabolic homeostasis. Eosinophils are associated with helminth immunity and allergy, often in conjunction with alternatively activated macrophages (AAMs). Adipose tissue AAMs are necessary to maintain glucose homeostasis and are induced by the cytokine interleukin-4 (IL-4). Here, we show that eosinophils are the major IL-4–expressing cells in white adipose tissues of mice, and, in their absence, AAMs are greatly attenuated. Eosinophils migrate into adipose tissue by an integrin-dependent process and reconstitute AAMs through an IL-4– or IL-13–dependent process. Mice fed a high-fat diet develop increased body fat, impaired glucose tolerance, and insulin resistance in the absence of eosinophils, and helminth-induced adipose tissue eosinophilia enhances glucose tolerance. Our results suggest that eosinophils play an unexpected role in metabolic homeostasis through maintenance of adipose AAMs.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/53e3b9af7348b7a2e45ce0521d6ac1736dcb6195

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Haiming Cao
2. R. Locksley
3. S. Kajimura
4. S. V. Van Dyken
5. B. Spiegelman
6. A. Chawla
7. TA Wynn
8. Jerrold M. Olefsky

In Immunology

1. R. Locksley
2. TA Wynn
3. S. V. Van Dyken
4. A. Chawla
5. Haiming Cao
6. B. Spiegelman
7. P. Murray
8. S. Galli

Citations in the corpus

• Adipocytokines in Obesity and Metabolic Disease (2014, positive): “Following macrophages, nearly every major type of immune cell has been identified in adipose tissue in recent years (Feuerer et al. 2009, Liu et al. 2009, Winer et al. 2009, Wu et al. 2011) and is actively involved in the endocrine function of adipose tissue in systemic metabolic regulation.”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Innate Immunity Innate immune pathways are known to control adipose tissue function and systemic glucose homeostasis (Molofsky et al., 2013; Wu et al., 2011).”
• Macrophage-mediated inflammation in metabolic disease (2011, background): “Using 4get reporter mice , Wu and colleagues found that 90% of the cells competent for IL-4 secretion in the adipose tissue of lean mice were eosinophils, and their presence in adipose tissue was inversely correlated with body mas”
• Macrophage polarization: An opportunity for improved outcomes in biomaterials and regenerative medicine (2012, background): “It has been suggested that local IL-4 producing eosinophils may be required for maintenance of this polarized M2 state [68].”
• Adipokines Mediate Inflammation and Insulin Resistance (2013, background): “In addition, mast cells (Liu et al., 2009), eosinophils (Wu et al., 2011), and dendritic cells (Bertola et al., 2012) are also critically involved in obesity-induced inflammation and insulin resistance through the production of pro- and anti-inflammatory cytokines in adipose tissues.”
• Cellular and Molecular Players in Adipose Tissue Inflammation in the Development of Obesity-induced Insulin Resistance (2013, neutral): “Furthermore, the eosinophil number decreases in ΔdblGATA mice exacerbate obesity-induced insulin resistance, while increases in eosinophils due to overexpression of IL-5 or helminth infections improve obesity-induced insulin resistance [76].”
• Eosinophils: changing perspectives in health and disease (2012, background): “The eosinophil granule proteins MBP, eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) activate mast cells, resulting in the release of histamine.”
• INTERLEUKIN-4- AND INTERLEUKIN-13-MEDIATED ALTERNATIVELY ACTIVATED MACROPHAGES: ROLES IN HOMEOSTASIS AND DISEASE (2013, neutral): “This regulation may exert reciprocal effects, as genetic deficiency of eosinophils also impairs accumulation of AAMs in white adipose tissue (WAT) (116).”
• What We Talk About When We Talk About Fat (2014, neutral): “Conversely, eosinophils and innate lymphoid (ILC2) cells act to reduce inflammation and thus restore insulin sensitivity (Molofsky et al., 2013; Wu et al., 2011).”