{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Apolipoprotein B receptor (APOBR), frequently referred to as the apoB48 receptor (APOB48R), is a multifunctional cell‐surface protein primarily expressed in reticuloendothelial cells—including monocytes, macrophages, and endothelial cells—and in adipose tissue. It mediates the binding and internalization of apoB48‐containing triglyceride‐rich lipoproteins (TRLs), such as chylomicrons, very low‐density lipoproteins, and their remnants, thereby promoting intracellular lipid accumulation and foam cell formation in atherosclerotic lesions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In monocyte-derived macrophages, nuclear receptor activation—particularly via peroxisome proliferator-activated receptors (PPARα and PPARγ)—can downregulate APOBR expression, thereby diminishing TRL-induced lipid uptake and suggesting an antiatherogenic mechanism"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic variations in the APOBR gene have been linked to altered plasma cholesterol levels and may influence susceptibility to metabolic disorders such as obesity, hypothyroidism, and atherosclerosis through modulation of lipid homeostasis and energy balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, dysregulation or polymorphisms in APOBR have been associated with increased risk for non‐cardiovascular conditions—including pneumonia and certain cancers—underscoring broader roles in inflammatory responses and cellular metabolism"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In bovine models, APOBR variants correlate with differences in lipid metabolite profiles and predisposition to subclinical ketosis during early lactation, indicating that APOBR-mediated uptake of phosphatidylcholine from low-density lipoproteins contributes to metabolic stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, studies in human cells have shown that dietary fatty acid composition in postprandial TRLs can modulate APOBR transcription and subsequent lipid uptake in monocytes and macrophages—processes that involve PPAR–retinoid X receptor signaling and may be targeted to prevent excessive lipid accumulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, modulation of APOBR expression by bioactive compounds such as curcumin further supports its multifaceted role in regulating lipid metabolism and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these observations highlight APOBR as a central mediator linking dietary lipid uptake, genetic variation, and intracellular lipid accumulation with downstream effects on inflammation and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akio Kawakami, Mariko Tani, Tsuyoshi Chiba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pitavastatin inhibits remnant lipoprotein-induced macrophage foam cell formation through ApoB48 receptor-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000152632.48937.2d"}], "href": "https://doi.org/10.1161/01.ATV.0000152632.48937.2d"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15591219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15591219"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M L Brown, M P Ramprasad, P K Umeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A macrophage receptor for apolipoprotein B48: cloning, expression, and atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.120184097"}], "href": "https://doi.org/10.1073/pnas.120184097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10852956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10852956"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A Tanaka "}, {"type": "b", "children": [{"type": "t", "text": "[Human apolipoprotein B48 receptor]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nihon Rinsho (1999)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10638201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10638201"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Matthew L Brown, Katsumasa Yui, Jonathan D Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The murine macrophage apoB-48 receptor gene (Apob-48r): homology to the human receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12177162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12177162"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Akira Tanaka "}, {"type": "b", "children": [{"type": "t", "text": "Postprandial hyperlipidemia and atherosclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Atheroscler Thromb (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5551/jat.11.322"}], "href": "https://doi.org/10.5551/jat.11.322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15644585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15644585"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Beatriz Bermudez, Sergio Lopez, Lourdes M Varela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Triglyceride-rich lipoprotein regulates APOB48 receptor gene expression in human THP-1 monocytes and macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3945/jn.111.149963"}], "href": "https://doi.org/10.3945/jn.111.149963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22190030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22190030"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Go Haraguchi, Yasushi Kobayashi, Matthew L Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPAR(alpha) and PPAR(gamma) activators suppress the monocyte-macrophage apoB-48 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M300077-JLR200"}], "href": "https://doi.org/10.1194/jlr.M300077-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12700342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12700342"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yuko Fujita, Yoichi Ezura, Hideaki Bujo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-005-0240-1"}], "href": "https://doi.org/10.1007/s10038-005-0240-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15830122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15830122"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jianhua Sun, Lizhi Sun, Weijie Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A family with hypothyroidism caused by fatty acid synthase and apolipoprotein B receptor mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2018.9499"}], "href": "https://doi.org/10.3892/mmr.2018.9499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30272292"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30272292"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Juan R González, Alejandro Cáceres, Tonu Esko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A common 16p11.2 inversion underlies the joint susceptibility to asthma and obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2014.01.015"}], "href": "https://doi.org/10.1016/j.ajhg.2014.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24560518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24560518"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Wuping Liu, Jingjing Xu, Tao Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An integrating strategy for serum metabolomics and microarray analysis to expand the understanding of diet-induced obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anal Methods (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1039/d1ay00821h"}], "href": "https://doi.org/10.1039/d1ay00821h"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34180923"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34180923"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Adrian I Campos, Pik Kho, Karla X Vazquez-Prada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Susceptibility to Pneumonia: A GWAS Meta-Analysis Between the UK Biobank and FinnGen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Twin Res Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/thg.2021.27"}], "href": "https://doi.org/10.1017/thg.2021.27"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34340725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34340725"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Imen Hemissi, Sami Boussetta, Hamza Dallali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Development of a custom next-generation sequencing panel for the determination of bladder cancer risk in a Tunisian cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-021-06951-4"}], "href": "https://doi.org/10.1007/s11033-021-06951-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34854013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34854013"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "S Nayeri, F Schenkel, A Fleming, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analysis for β-hydroxybutyrate concentration in Milk in Holstein dairy cattle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12863-019-0761-9"}], "href": "https://doi.org/10.1186/s12863-019-0761-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31311492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31311492"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "H Huang, J Cao, Q Hanif, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies energy metabolism genes for resistance to ketosis in Chinese Holstein cattle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anim Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/age.12802"}], "href": "https://doi.org/10.1111/age.12802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31179571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31179571"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jens Tetens, Claas Heuer, Iris Heyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.00126.2014"}], "href": "https://doi.org/10.1152/physiolgenomics.00126.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25670729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25670729"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Anna M Palmer, Esther Nova, Eliz Anil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential uptake of subfractions of triglyceride-rich lipoproteins by THP-1 macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2004.12.038"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2004.12.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15910848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15910848"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Carey N Lumeng, Stephanie M Deyoung, Jennifer L Bodzin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db06-1076"}], "href": "https://doi.org/10.2337/db06-1076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17192460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17192460"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Lourdes M Varela, Almudena Ortega-Gomez, Sergio Lopez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effects of dietary fatty acids on the postprandial triglyceride-rich lipoprotein/apoB48 receptor axis in human monocyte/macrophage cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Nutr Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jnutbio.2013.07.004"}], "href": "https://doi.org/10.1016/j.jnutbio.2013.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24231096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24231096"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Mingjie Zhou, Chunlei Fan, Nan Tian "}, {"type": "b", "children": [{"type": "t", "text": "Effects of curcumin on the gene expression profile of L-02 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/br.2015.460"}], "href": "https://doi.org/10.3892/br.2015.460"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26171159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26171159"}]}]}]}