Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis

By K. Nguyen, Yifu Qiu, Xiaojin Cui, Y. Goh, J. Mwangi, Tovo David, Lata Mukundan, F. Brombacher, R. Locksley, A. Chawla. Nature, 2011

1,024 citations recorded by the source corpus.

All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release of noradrenaline in brown adipose tissue and white adipose tissue. Acting via the β3-adrenergic receptors, noradrenaline induces lipolysis in white adipocytes, whereas it stimulates the expression of thermogenic genes, such as PPAR-γ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1), in brown adipocytes. However, the precise nature of all the cell types involved in this efferent loop is not well established. Here we report in mice an unexpected requirement for the interleukin-4 (IL-4)-stimulated program of alternative macrophage activation in adaptive thermogenesis. Exposure to cold temperature rapidly promoted alternative activation of adipose tissue macrophages, which secrete catecholamines to induce thermogenic gene expression in brown adipose tissue and lipolysis in white adipose tissue. Absence of alternatively activated macrophages impaired metabolic adaptations to cold, whereas administration of IL-4 increased thermogenic gene expression, fatty acid mobilization and energy expenditure, all in a macrophage-dependent manner. Thus, we have discovered a role for alternatively activated macrophages in the orchestration of an important mammalian stress response, the response to cold.

Subfields: Epidemiology, Physiology, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/9a6c01e7c898d0ef0722c6ffad5626edc3e078ff

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. B. Spiegelman
3. S. Kajimura
4. R. Locksley
5. A. Chawla
6. L. Sidossis
7. S. V. Van Dyken
8. E. Rosen

In Physiology

1. S. Kajimura
2. B. Spiegelman
3. L. Sidossis
4. P. Seale
5. Haiming Cao
6. E. Rosen
7. A. Chawla
8. R. Locksley

In Rehabilitation

1. S. Kajimura
2. L. Sidossis
3. B. Spiegelman
4. P. Seale
5. J. Hawley
6. Haiming Cao
7. R. Medzhitov
8. Tamás Rőszer

Citations in the corpus

• Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, positive): “When activated by eosinophils via IL-4 and IL-13 signaling, M2 macrophages are recruited to subcutaneous WAT and secrete catecholamines to activate WAT browning (54, 55).”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Upon cold exposure, NE may be released from the sympathetic nerve or M2 macrophages to activate the BAT/beige fat thermogenic program (Nguyen et al., 2011; Young et al., 1982).”
• Macrophages Facilitate Electrical Conduction in the Heart (2017, neutral): “For instance, macrophages contribute to thermogenesis regulation in adipose tissue (Nguyen et al., 2011), iron recycling in the spleen and liver (Theurl et al., 2016), and synaptic pruning in the brain (Paolicelli et al., 2011).”
• Adipocytokines in Obesity and Metabolic Disease (2014, positive): “For examples, M2 macrophages produce catecholamines that sustain adaptive thermogenesis (Nguyen et al. 2011), and lipolysis during fasting recruits macrophages that buffer local lipid increase and protect adipose function (Kosteli et al. 2010).”
• Macrophage Polarization in Inflammatory Diseases (2014, background): “Adaptation to cold temperature promoted the ATM to the alternative activation state, which secreted catecholamines to induce the expression of thermogenic genes including PPARγ coactivator 1a (Ppargc1a), uncoupling protein 1 (Ucp1) and acyl-CoA synthetase long-chain family member 1 (Acsl1) in brown ”
• Stress, Inflammation, and Defense of Homeostasis (2014, background): “…nociceptors may monitor and control tissue homeostasis not only at the extremes of infection and injury, but also duringmore common and less dramatic alterations of normal tissue states (Ahern, 2013; Basbaum et al., 2009;Mosser and Edwards, 2008; Nguyen et al., 2011; Pollard, 2009; Tracey, 2009).”
• JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. (2012, background): “Very recently, AAMs and STAT6 have been implicated in the mammalian thermogenic Immunity 36, April 20, 2012 ª2012 Elsevier Inc. 543 response (Nguyen et al., 2011).”
• Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms (2015, background): “The M2 macrophages are sources of neurotransmitters and hormones, such as catecholamines [120], substance P [121], adiponectin [122], and growth factors [123].”
• A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. (2014, background): “Interestingly, alternatively activated macrophages sustain adaptive thermogenesis in BAT through enhanced recruitment of b-adrenergic fibers (Nguyen et al., 2011).”
• 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).”
• From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation (2014, neutral): “thermogenesis (134) Obesity, diabetes, insulin resistance, loss”