title: Hepatocytes Are the Principal Source of Circulating RBP4 in Mice.
abstract: RBP4 is produced mainly by hepatocytes. In type 2 diabetes and obesity, circulating RBP4 is increased and may act systemically to cause insulin resistance and glucose intolerance. Observations that adipocyte RBP4 mRNA increases in parallel with circulating RBP4 in these conditions, whereas liver RBP4 mRNA does not, led to a widely held hypothesis that elevated circulating RBP4 is a direct result of increased production by adipocytes. To test this, we generated mice with hepatocyte-specific deletion of RBP4 (liver RBP4 knockout or LRKO mice). Adipose tissue RBP4 expression and secretion remained intact in LRKO mice and increased as expected in the setting of diet-induced insulin resistance. However, circulating RBP4 was undetectable in LRKO mice. We conclude that adipocyte RBP4 is not a significant source of circulating RBP4, even in the setting of insulin resistance. Adipocyte RBP4, therefore, may have a more important autocrine or paracrine function that is confined within the adipose tissue compartment.
authors: Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, UT.
authors: Spencer J
authors: SJ
authors: Thompson
authors: Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, UT.|George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT.
authors: Ashot
authors: A
authors: Sargsyan
authors: Department of Medicine and Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY.
authors: Seung-Ah
authors: SA
authors: Lee
authors: Department of Medicine and Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY.
authors: Jason J
authors: JJ
authors: Yuen
authors: Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, UT.|George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT.
authors: Jinjin
authors: J
authors: Cai
authors: George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT.
authors: Rana
authors: R
authors: Smalling
authors: Département de Génétique Fonctionnelle et Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire; Centre National de la Recherche Scientifique; INSERM; and Université de Strasbourg, Illkirch, France.
authors: Norbert
authors: N
authors: Ghyselinck
authors: Département de Génétique Fonctionnelle et Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire; Centre National de la Recherche Scientifique; INSERM; and Université de Strasbourg, Illkirch, France.|Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors: Manuel
authors: M
authors: Mark
authors: Department of Medicine and Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY.
authors: William S
authors: WS
authors: Blaner
authors: Molecular Medicine Program, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Nutrition, and Department of Biological Chemistry, University of Utah School of Medicine, Salt Lake City, UT tim.graham@progenitorlifesciences.com.|George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT.
authors: Timothy E
authors: TE
authors: Graham
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D005260:Female; D005838:Genotype; D022781:Hepatocytes / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; C502487:Rbp4 protein, mouse; D054839:Retinol-Binding Proteins, Plasma