Neuropeptide Y is produced by adipose tissue macrophages and regulates obesity-induced inflammation

• Published in: PloS one Vol. 8; no. 3; p. e57929
• Main Authors: Singer, Kanakadurga, Morris, David L, Oatmen, Kelsie E, Wang, Tianyi, DelProposto, Jennifer, Mergian, Taleen, Cho, Kae Won, Lumeng, Carey N
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-03-2013; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipose tissue; Adipose Tissue - cytology; Animal tissues; Animals; Autocrine signalling; Biology; Body fat; Bone marrow; CD11c antigen; Cell activation; Chimeras; Cytokines; Dendritic cells; Dendritic Cells - cytology; Diabetes; Diet; Gene Expression Regulation; Hematopoietic Stem Cells - cytology; High fat diet; Inflammation; Inflammation - metabolism; Insulin Resistance; Interleukin 6; Interleukin-6 - metabolism; Lipopolysaccharides; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; Medical schools; Medicine; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Obese; Monocytes; Monocytes - cytology; Myeloid cells; Neuropeptide Y; Neuropeptide Y - metabolism; Neuropeptides; Obesity; Obesity - metabolism; Paracrine signalling; Pediatrics; Receptors, Neuropeptide Y - metabolism; Rodents; Stress; Triglycerides - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Weight control; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057929

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 Ly6c(hi) 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.