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Obesity: a neuroimmunometabolic perspective

Abstract

Neuroimmunology and immunometabolism are burgeoning topics of study, but the intersection of these two fields is scarcely considered. This interplay is particularly prevalent within adipose tissue, where immune cells and the sympathetic nervous system (SNS) have an important role in metabolic homeostasis and pathology, namely in obesity. In the present Review, we first outline the established reciprocal adipose–SNS relationship comprising the neuroendocrine loop facilitated primarily by adipose tissue-derived leptin and SNS-derived noradrenaline. Next, we review the extensive crosstalk between adipocytes and resident innate immune cells as well as the changes that occur in these secretory and signalling pathways in obesity. Finally, we discuss the effect of SNS adrenergic signalling in immune cells and conclude with exciting new research demonstrating an immutable role for SNS-resident macrophages in modulating SNS–adipose crosstalk. We posit that the latter point constitutes the existence of a new field — neuroimmunometabolism.

Key points

  • Adipose tissue is innervated by sympathetic nerves that release noradrenaline, which drives thermogenesis in brown adipose tissue and lipolysis and/or beiging in white adipose tissue.

  • Adipocytes release leptin and other adipokines that signal through the hypothalamus to control whole-body metabolism, including modulation of sympathetic output to adipose tissue.

  • The polarization of adipose-resident macrophages is a prominent effector in obesity and insulin resistance. This polarization is sensitive to signalling from other immune cells, adipocytes and sympathetic nerves.

  • Adipokines, such as leptin and adiponectin, directly modulate the activation status of macrophages and other immune cells. Adipokine release changes drastically in obesity.

  • Noradrenaline released by sympathetic nerves directly modulates macrophages and other immune cells by signalling through various subtypes of adrenoreceptor.

  • Small populations of macrophages have been discovered by several groups in various adipose depots that closely associate with sympathetic nerves and play a novel role in modulating sympathetic innervation of adipose tissue.

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Fig. 1: Neuroimmunometabolic triad.
Fig. 2: Hypothalamic–SNS fat loop.
Fig. 3: Adipose–immune communication.
Fig. 4: Sympathetic neuron-associated macrophages in adipose tissue.

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All authors researched data for the article, contributed to discussion of the content, C.M.L. wrote the article and C.M.L. and A.I.D. reviewed and/or edited the article before submission.

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Correspondence to Ana I. Domingos.

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Arborizations

Tree-like, branching arrangement of neuronal processes.

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Larabee, C.M., Neely, O.C. & Domingos, A.I. Obesity: a neuroimmunometabolic perspective. Nat Rev Endocrinol 16, 30–43 (2020). https://doi.org/10.1038/s41574-019-0283-6

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