{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent evidence indicates that the cytokine‐like protein FAM19A5 plays a pivotal role in bone homeostasis. Specifically, studies have shown that FAM19A5 acts as an inhibitor of osteoclastogenesis. It promotes chemotactic migration of bone marrow‐derived macrophages while markedly suppressing the induction of osteoclast-related genes (e.g., RANK, TRAF6, OSCAR, TRAP, Blimp1, c‐fos, and NFATc1) by RANKL, in parallel with upregulating negative regulators such as MafB and IRF-8. This inhibitory effect on osteoclast formation is mediated by the receptor FPR2, positioning FAM19A5 as a novel endogenous ligand capable of modulating bone resorption processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "Recent findings also suggest that FAM19A5 functions as an adipokine involved in obesity-related cardiovascular pathology. Although originally predicted to be distantly related to the CC-chemokine family, adipose-derived FAM19A5 has been implicated in regulating vascular injury responses, thereby providing a molecular link between obesity and cardiovascular diseases. This novel role for FAM19A5 highlights its potential as a therapeutic target for mitigating vascular complications associated with obesity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "Moreover, FAM19A5 is highly expressed within the central nervous system, particularly in hypothalamic cells—including neurons expressing proopiomelanocortin (POMC) and neuropeptide Y/agouti-related peptide, as well as in microglia. Inflammatory stimulation with tumor necrosis factor-α (TNF-α) robustly upregulates FAM19A5 in the hypothalamus. Experimental manipulation of FAM19A5 levels demonstrates that it contributes to cytokine-induced sickness responses, such as anorexia, weight loss, and hyperthermia, possibly through the activation of inflammatory factors and POMC neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Min Young Park, Hyung Sik Kim, Mingyu Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM19A5, a brain-specific chemokine, inhibits RANKL-induced osteoclast formation through formyl peptide receptor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-15586-0"}], "href": "https://doi.org/10.1038/s41598-017-15586-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29138422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29138422"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yingbao Wang, Dixin Chen, Yan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through Sphingosine-1-Phosphate Receptor 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.117.032398"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.117.032398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29453251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29453251"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dasol Kang, Han Rae Kim, Kwang Kon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Brain-specific chemokine FAM19A5 induces hypothalamic inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.12.119"}], "href": "https://doi.org/10.1016/j.bbrc.2019.12.119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31954515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31954515"}]}]}]}