Neuropeptide Y Is Produced by Adipose Tissue Macrophages and Regulates Obesity-Induced Inflammation

Abstract

Neuropeptide Y (NPY) is induced in peripheral tissues such as adipose tissue with obesity. The mechanism and function of NPY induction in fat are unclear. Given the evidence that NPY can modulate inflammation, we examined the hypothesis that NPY regulates the function of adipose tissue macrophages (ATMs) in response to dietary obesity in mice. NPY was induced by dietary obesity in the stromal vascular cells of visceral fat depots from mice. Surprisingly, the induction of Npy was limited to purified ATMs from obese mice. Significant basal production of NPY was observed in cultured bone marrow derived macrophage and dendritic cells (DCs) and was increased with LPS stimulation. In vitro, addition of NPY to myeloid cells had minimal effects on their activation profiles. NPY receptor inhibition promoted DC maturation and the production of IL-6 and TNFα suggesting an anti-inflammatory function for NPY signaling in DCs. Consistent with this, NPY injection into lean mice decreased the quantity of M1-like CD11c+ ATMs and suppressed Ly6chi monocytes. BM chimeras generated from Npy−/− donors demonstrated that hematopoietic NPY contributes to the obesity-induced induction of Npy in fat. In addition, loss of Npy expression from hematopoietic cells led to an increase in CD11c+ ATMs in visceral fat with high fat diet feeding. Overall, our studies suggest that NPY is produced by a range of myeloid cells and that obesity activates the production of NPY in adipose tissue macrophages with autocrine and paracrine effects.

The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD)

“…NPY is produced by T lymphocytes, macrophages, monocytes, and dendritic cells during inflammation, and it modulates the immune cell activities via a paracrine or autocrine mode of action (Macia et al 2012;Schwarz et al 1994;Wheway et al 2005). The Y 1 and Y 2 receptors are localized on immune cells including macrophages, neutrophils, granulocytes, and lymphocytes, with the Y 1 receptor being the most abundant (Bedoui et al 2008;Chandrasekharan et al 2013b;Dimitrijevic et al 2005;Dimitrijevic and Stanojevic 2013;Dimitrijevic et al 2010;Singer et al 2013). The binding of NPY to these receptors influences the activities of the immune cells Petitto et al 1994) in either a pro-or an anti-inflammatory manner Wheway et al 2005).…”

Extracellular molecules in hematopoietic stem cell mobilisation

“…The source of neuropeptide Y has not been firmly established. Although it is produced by sympathetic neurones [106], other bone marrow cells, including myeloid cells and bone marrow-derived macrophages, [107] also synthesize neuropeptide Y.…”

Recent advances in the understanding of how neuropeptide Y andα-melanocyte stimulating hormone function in adipose physiology

“…124 Adipose-specific production of NPY5R remains debated, as it has been detected in the adipose of rodents 125,126 and chickens, 67 but at other times is undetectable. 127,128 Additionally, NPY2R was expressed in human, 10 mouse 10 and chicken preadipocytes, 11 while in another study NPY2R was not detected in mouse preadipocytes. 128 While in vivo studies may show the importance of each receptor in whole body adipose biology, in vitro studies allow more specific quantification and study of regulation in a particular cell type.…”