Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat

By Yifu Qiu, K. Nguyen, J. Odegaard, Xiaojin Cui, Xiaoyu Tian, R. Locksley, R. Palmiter, A. Chawla. Cell, 2014

810 citations recorded by the source corpus.

SUMMARY Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13 and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat. Mechanistically, macrophages recruited to cold-stressed subcutaneous white adipose tissue (scWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production, factors required for browning of scWAT. Conversely, administration of IL-4 to thermoneutral mice increases beige fat mass and thermogenic capacity to ameliorate pre-established obesity. Together, our findings have uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its targeting to treat obesity.

Subfields: Epidemiology, Physiology, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/25ff3adb207304cb1c13c8b7341cff5beff8707f

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. R. Locksley
2. S. Kajimura
3. B. Spiegelman
4. A. Chawla
5. L. Sidossis
6. J. Odegaard
7. P. Seale
8. P. Murray

In Physiology

1. S. Kajimura
2. L. Sidossis
3. P. Seale
4. B. Spiegelman
5. R. Locksley
6. A. Chawla
7. J. Odegaard
8. Lata Mukundan

In Rehabilitation

1. S. Kajimura
2. L. Sidossis
3. B. Spiegelman
4. P. Seale
5. P. Murray
6. Tamás Rőszer

Citations in the corpus

• Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, positive): “Conversely, IL-4 administration was sufficient to induce WAT browning and reduce diet-induced body weight gain (55).”
• Macrophage Polarization. (2017, background): “For example, TNF suppresses the ability of macrophages to contribute to healing damage in the spinal cord and is vital for the suppression of the normal homeostatic M2-like macrophages in adipose tissue (76, 77).”
• Adipose tissue plasticity in health and disease (2022, background): “Type 2 cytokines, especially IL-4, promote beige-fat biogenesis and ameliorate obesity, although the mechanisms involved remain uncertain (Fischer et al., 2017; Henriques et al., 2020; Qiu et al., 2014).”
• Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis (2014, positive): “demonstrated that type 2 activation of macrophages via IL4Ra stimulates release of norepinephrine in the scWAT and eWAT of mice (Nguyen et al., 2011; Qiu et al., 2014), we next asked whether myeloid cell IL-4Ra signaling might regulate the postnatal expansion and commitment of APs to the beige adipo”
• Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms (2015, background): “Catecholamines produced by adipose tissue macrophages have metabolic impact, by promoting brown adipose tissue differentiation and adaptive thermogenesis in the mouse [120, 124].”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Mice that lacked IL4 signaling or the capacity to produce catecholamines selectively in macrophages appeared to have an impaired beige adipocyte development under cold (Qiu et al., 2014).”
• Adiponectin Regulation and Function (2018, positive): “Indirectly, adiponectin increases the proliferation of M2 macrophages, which enhance thermogenic remodeling in subcutaneous WAT by stimulating the production of catecholamines (115, 264).”
• Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders (2016, background): “Chawla’s group proposed that M2 ATMs induce thermogenic tissue remodeling by amplifying cold-induced β-adrenergic signaling via local catecholamine production (196, 198).”