The paper, ‘Immunomodulatory Leptin Receptor+ Sympathetic Perineurial Barrier Cells Protect Against Obesity by Facilitating Brown Adipose Tissue Thermogenesis’ covers research that reveals a cellular target unifying the neuroendocrine and immunometabolic regulation of adipose tissue homeostasis, which could be targeted therapeutically to mitigate obesity.
This research looks at Adipose tissues (ATs) which are innervated by sympathetic nerves, and in turn drive reduction of fat mass via lipolysis and thermogenesis. Researchers identified a population of immunomodulatory leptin receptor+ (LepR+) Sympathetic Perineurial Barrier Cells (SPCs) present in mice and humans, which uniquely co-express Lepr and Interleukin-33 (Il33) and ensheath adipose tissue sympathetic axon bundles.
Brown adipose tissues (BAT) of mice lacking IL-33 in SPCs (SPCΔIl33) had fewer Treg cells and eosinophils, resulting in increased BAT inflammation. This means that SPCΔIl33 mice were more susceptible to diet-induced obesity, independently of food intake. Furthermore, SPCΔIl33 mice had impaired adaptive thermogenesis, and were unresponsive to leptin-induced rescue of metabolic adaptation.
Ana Domingos says, ‘We, therefore, identify LepR+ SPCs as a source of IL-33 which orchestrate an anti-inflammatory BAT environment, preserving sympathetic-mediated thermogenesis and body weight homeostasis. LepR+IL-33+ SPCs provide a cellular link between leptin and immune regulation of body weight’.
Emma Haberman comments, ‘Here we show that the production of anti-inflammatory IL-33 by LepR+ perineurial cells acts as a ‘brake’ on the adipose tissue neuroinflammation that is usually associated with obesity.’
This research is particularly important because it demonstrates a link between neuroendocrinology and immunometabolism, which have previously been disconnected fields of obesity research.
Read the paper here