{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRetinol‐binding protein 4 (RBP4) is a multifunctional protein best recognized for its role in transporting retinol (vitamin A) in circulation and as an adipokine linking obesity to metabolic dysfunction. RBP4 is secreted primarily by hepatocytes and adipocytes, and its circulating levels have been associated with insulin resistance, type 2 diabetes, and components of the metabolic syndrome. Elevated RBP4 concentrations correlate with increased adiposity—including marked expression in visceral fat—and with altered glucose uptake in human and animal studies, suggesting that RBP4 serves as an important biochemical bridge between excess fat accumulation and impaired metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in retinol transport, RBP4 has emerged as a modulator of cellular signaling and inflammation. Experimental studies have demonstrated that RBP4 can activate innate immune pathways—engaging antigen‐presenting cells and driving CD4 T cell polarization—as well as impair insulin signaling in adipocytes by interfering with key phosphorylation events. In addition, through its interaction with the STRA6 receptor and, in certain tissues, with a newly identified transporter (RBPR2), RBP4 facilitates the uptake of retinol, thereby integrating vitamin A delivery with cytokine receptor signaling and proinflammatory responses. These effects occur independently of retinol binding status, suggesting that RBP4 per se may trigger inflammation in vascular endothelial and other cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its metabolic and inflammatory functions, genetic and clinical investigations have linked RBP4 to a broad spectrum of disease states. Variants in the RBP4 gene and altered expression levels have been associated with type 2 diabetes susceptibility, nonalcoholic fatty liver disease, cardiovascular disease, and even certain cancers. Furthermore, research has shown that RBP4 levels may be modulated by interventions such as weight loss, dietary changes, and exercise, although its role as a therapeutic target remains controversial. These studies also underscore that aberrant RBP4 signaling—whether through changes in its retinol‐binding capacity or via its interaction with other proteins like transthyretin—can contribute to impaired insulin signaling, hepatic retinol homeostasis, vascular inflammation, and clinical outcomes in metabolic disorders. Collectively, these diverse findings highlight RBP4 not only as a key physiological mediator of vitamin A transport but also as a potential biomarker and mechanistic actor in metabolic and inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "49"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Young Min Cho, Byung-Soo Youn, Hyewon Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc06-0360"}], "href": "https://doi.org/10.2337/dc06-0360"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17065684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17065684"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nora Klöting, Timothy E Graham, Janin Berndt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2007.06.002"}], "href": "https://doi.org/10.1016/j.cmet.2007.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17618858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17618858"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jürgen Janke, Stefan Engeli, Michael Boschmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 in human obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db06-0616"}], "href": "https://doi.org/10.2337/db06-0616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17003346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17003346"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Aiwei Yao-Borengasser, Vijayalakshmi Varma, Angela M Bodles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol binding protein 4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-0816"}], "href": "https://doi.org/10.1210/jc.2006-0816"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17595259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17595259"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dominik G Haider, Karin Schindler, Gerhard Prager, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-1839"}], "href": "https://doi.org/10.1210/jc.2006-1839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17164313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17164313"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Primoz Kotnik, Pamela Fischer-Posovszky, Martin Wabitsch "}, {"type": "b", "children": [{"type": "t", "text": "RBP4: a controversial adipokine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Endocrinol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/EJE-11-0431"}], "href": "https://doi.org/10.1530/EJE-11-0431"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21835764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21835764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Norbert Stefan, Anita M Hennige, Harald Staiger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc06-2342"}], "href": "https://doi.org/10.2337/dc06-2342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17259477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17259477"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shai Gavi, Louise M Stuart, Patricia Kelly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-1815"}], "href": "https://doi.org/10.1210/jc.2006-1815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17299074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17299074"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Pedro M Moraes-Vieira, Mark M Yore, Peter M Dwyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2014.01.018"}], "href": "https://doi.org/10.1016/j.cmet.2014.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24606904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24606904"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "M von Eynatten, P M Lepper, D Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-007-0743-8"}], "href": "https://doi.org/10.1007/s00125-007-0743-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17639305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17639305"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Andrea Isken, Marcin Golczak, Vitus Oberhauser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2008.01.009"}], "href": "https://doi.org/10.1016/j.cmet.2008.01.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18316031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18316031"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Krysten M Farjo, Rafal A Farjo, Stacey Halsey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 induces inflammation in human endothelial cells by an NADPH oxidase- and nuclear factor kappa B-dependent and retinol-independent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00820-12"}], "href": "https://doi.org/10.1128/MCB.00820-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23071093"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23071093"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Weiping Jia, Haiya Wu, Yuqian Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of serum retinol-binding protein 4 and visceral adiposity in Chinese subjects with and without type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-0209"}], "href": "https://doi.org/10.1210/jc.2007-0209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17550959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17550959"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Anita Ost, Anna Danielsson, Martin Lidén, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein-4 attenuates insulin-induced phosphorylation of IRS1 and ERK1/2 in primary human adipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-8173com"}], "href": "https://doi.org/10.1096/fj.07-8173com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17575262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17575262"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Anke Tönjes, Mathias Fasshauer, Jürgen Kratzsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0013911"}], "href": "https://doi.org/10.1371/journal.pone.0013911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21085476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21085476"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Philomena Alapatt, Fangjian Guo, Susan M Komanetsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver retinol transporter and receptor for serum retinol-binding protein (RBP4)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.369132"}], "href": "https://doi.org/10.1074/jbc.M112.369132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23105095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23105095"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Qi Sun, Urban A Kiernan, Ling Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma retinol-binding protein 4 (RBP4) levels and risk of coronary heart disease: a prospective analysis among women in the nurses' health study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.113.002073"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.113.002073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23584360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23584360"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Erik Ingelsson, Johan Sundström, Håkan Melhus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2009.02.029"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2009.02.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19339013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19339013"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Lkhagvasuren Munkhtulga, Kazuhiro Nakayama, Nanami Utsumi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-006-0264-4"}], "href": "https://doi.org/10.1007/s00439-006-0264-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17006670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17006670"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Miguel L Soares, Teresa Coelho, Alda Sousa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Susceptibility and modifier genes in Portuguese transthyretin V30M amyloid polyneuropathy: complexity in a single-gene disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi051"}], "href": "https://doi.org/10.1093/hmg/ddi051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15649951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15649951"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Andrea Henze, Simone K Frey, Jens Raila, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db08-0866"}], "href": "https://doi.org/10.2337/db08-0866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18796616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18796616"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Michaela Vitkova, Eva Klimcakova, Michaela Kovacikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2006-2668"}], "href": "https://doi.org/10.1210/jc.2006-2668"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17405846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17405846"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Theodore W K Ng, Gerald F Watts, P Hugh R Barrett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of weight loss on LDL and HDL kinetics in the metabolic syndrome: associations with changes in plasma retinol-binding protein-4 and adiponectin levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc07-0768"}], "href": "https://doi.org/10.2337/dc07-0768"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17686833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17686833"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Bee K Tan, Jing Chen, Hendrik Lehnert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raised serum, adipocyte, and adipose tissue retinol-binding protein 4 in overweight women with polycystic ovary syndrome: effects of gonadal and adrenal steroids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-0091"}], "href": "https://doi.org/10.1210/jc.2007-0091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17456573"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17456573"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Peter Kovacs, Michaela Geyer, Janin Berndt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db06-1647"}], "href": "https://doi.org/10.2337/db06-1647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17728376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17728376"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "J Raila, A Henze, J Spranger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ki.5002372"}], "href": "https://doi.org/10.1038/sj.ki.5002372"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17568782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17568782"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sheelarani Karunanithi, Liraz Levi, Jennifer DeVecchio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cell Reports (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stemcr.2017.06.002"}], "href": "https://doi.org/10.1016/j.stemcr.2017.06.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28689994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28689994"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Thomas Olsen, Rune Blomhoff "}, {"type": "b", "children": [{"type": "t", "text": "Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Nutr (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/advances/nmz131"}], "href": "https://doi.org/10.1093/advances/nmz131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31868199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31868199"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Michaela Ziegelmeier, Anette Bachmann, Jeannette Seeger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum levels of adipokine retinol-binding protein-4 in relation to renal function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc07-0275"}], "href": "https://doi.org/10.2337/dc07-0275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17630267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17630267"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Rebekah L Craig, Winston S Chu, Steven C Elbein "}, {"type": "b", "children": [{"type": "t", "text": "Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2006.11.003"}], "href": "https://doi.org/10.1016/j.ymgme.2006.11.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17174134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17174134"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Sascha Gerdes, Svetlana Osadtschy, Martin Rostami-Yazdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leptin, adiponectin, visfatin and retinol-binding protein-4 - mediators of comorbidities in patients with psoriasis?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0625.2011.01402.x"}], "href": "https://doi.org/10.1111/j.1600-0625.2011.01402.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22151390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22151390"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Thomas Reinehr, Birgit Stoffel-Wagner, Christian L Roth "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2007-2745"}], "href": "https://doi.org/10.1210/jc.2007-2745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18397979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18397979"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Y H Ku, K A Han, H Ahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Int Med Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/147323001003800305"}], "href": "https://doi.org/10.1177/147323001003800305"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20819415"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20819415"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "K M Choi, T N Kim, H J Yoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2008.03374.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2008.03374.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18710473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18710473"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Gang Liu, Ming Ding, Stephanie E Chiuve, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.116.308320"}], "href": "https://doi.org/10.1161/ATVBAHA.116.308320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27609367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27609367"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Haiya Wu, Weiping Jia, Yuqian Bao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Res Clin Pract (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.diabres.2007.08.016"}], "href": "https://doi.org/10.1016/j.diabres.2007.08.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17904683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17904683"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Lies Langouche, Sarah Vander Perre, Jan Frystyk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adiponectin, retinol-binding protein 4, and leptin in protracted critical illness of pulmonary origin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Crit Care (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/cc7956"}], "href": "https://doi.org/10.1186/cc7956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19589139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19589139"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Alykhan Motani, Zhulun Wang, Marion Conn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a non-retinoid ligand for retinol-binding protein 4 which lowers serum retinol-binding protein 4 levels in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M809654200"}], "href": "https://doi.org/10.1074/jbc.M809654200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19147488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19147488"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "M van Hoek, A Dehghan, M C Zillikens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An RBP4 promoter polymorphism increases risk of type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-008-1042-8"}], "href": "https://doi.org/10.1007/s00125-008-1042-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18496666"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18496666"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "K Krzyzanowska, L Zemany, W Krugluger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-008-1009-9"}], "href": "https://doi.org/10.1007/s00125-008-1009-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18437353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18437353"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Young Eun Jeon, Kyung Eun Lee, Ji Ann Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kisspeptin, leptin, and retinol-binding protein 4 in women with polycystic ovary syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gynecol Obstet Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000350217"}], "href": "https://doi.org/10.1159/000350217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23571154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23571154"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "J Gómez-Ambrosi, A Rodríguez, V Catalán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum retinol-binding protein 4 is not increased in obesity or obesity-associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2007.03156.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2007.03156.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18081728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18081728"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "G A Christou, A D Tselepis, D N Kiortsis "}, {"type": "b", "children": [{"type": "t", "text": "The metabolic role of retinol binding protein 4: an update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Horm Metab Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0031-1295491"}], "href": "https://doi.org/10.1055/s-0031-1295491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22205567"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22205567"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Ji-Won Lee, Jee-Aee Im, Hye-Ree Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Visceral adiposity is associated with serum retinol binding protein-4 levels in healthy women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Obesity (Silver Spring) (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/oby.2007.264"}], "href": "https://doi.org/10.1038/oby.2007.264"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17890490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17890490"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Naim Alkhouri, Rocio Lopez, Michael Berk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Gastroenterol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MCG.0b013e3181a0998d"}], "href": "https://doi.org/10.1097/MCG.0b013e3181a0998d"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19525859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19525859"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Jordan P Mills, Harold C Furr, Sherry A Tanumihardjo "}, {"type": "b", "children": [{"type": "t", "text": "Retinol to retinol-binding protein (RBP) is low in obese adults due to elevated apo-RBP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3181/0803-RM-94"}], "href": "https://doi.org/10.3181/0803-RM-94"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18641048"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18641048"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Christa Meisinger, Ina M Rückert, Wolfgang Rathmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4 is associated with prediabetes in adults from the general population: the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes Care (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/dc11-0118"}], "href": "https://doi.org/10.2337/dc11-0118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21617096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21617096"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Alexander Tschoner, Wolfgang Sturm, Julia Engl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinol-binding protein 4, visceral fat, and the metabolic syndrome: effects of weight loss."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Obesity (Silver Spring) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/oby.2008.391"}], "href": "https://doi.org/10.1038/oby.2008.391"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18719670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18719670"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "Simone K Frey, Britta Nagl, Andrea Henze, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids Health Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-511X-7-29"}], "href": "https://doi.org/10.1186/1476-511X-7-29"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18752671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18752671"}]}]}]}