Sympathetic Nerves Keep Up an Anti-Inflammatory State by Inhibiting Macrophage TNF-α Expression in Fat Tissue

Sympathetic Nerves Keep Up an Anti-Inflammatory State by Inhibiting Macrophage TNF-α Expression in Fat Tissue

New report, published in Endocrinology, implicates the activity of the sympathetic nervous system (SNS) and its β2-adrenoceptor signaling pathway in sustaining at low levels the production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α in macrophages of lean mice.

Pro-inflammatory macrophages play a key role in the pathogenesis of the systemic low-grade chronic inflammation, associated with obesity and insulin resistance (Angela Castoldi et al., Front Immunol, 2016, 6:637).

How resident macrophages’ function is regulated, in lean animals, remains poorly understood. It is known, however that the adipose tissue is heavily innervated by sympathetic/noradrenergic nerves.

The study in Endocrinology by Lijun Tang and colleagues from the National Institute for Physiological Sciences, Okazaki, Aichi, Japan indicates that sympathetic nerves, innervating adipose tissue, down-regulate local TNF-α secretion directly via an effect on β2-adrenoceptors expressed by macrophages. The study also demonstrates that the brain melanocortin pathway is involved in the regulation of the anti-inflammatory state in lean mice via SNS-related mechanisms.

The authors suggest that, in the fat tissue of lean animals, a longstanding suppression of the β-adrenoceptor function may keep the balance of anti-inflammatory versus inflammatory state towards anti-inflammation, and this effect is not related to impairment of thermogenic function.

The sympathetic nerve-immune system interface and the anti-inflammatory SNS impact on macrophages might be dysfunctional in obese animals, and perhaps, in humans with obesity.

Source: Endocrinology, 2015, 156:3680-94.
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Source: Cover Image: Model for the suppressive role of the SNS and β2-AR signaling in regulation of TNF-α gene expression in adipose tissue. From/Author(s): Endocrinology, 2015, 156:3680-94. Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages by Lijun Tang, Shiki Okamoto, Tetsuya Shiuchi, Chitoku Toda, Kazuyo Takagi, Tatsuya Sato, Kumiko Saito, Shigefumi Yokota, and Yasuhiko Minokoshi; Credit:; Public domain;

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