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Diabetes. 2017 Jan;66(1):58-63. doi: 10.2337/db16-0286. Epub 2016 Oct 19.

Hepatocytes Are the Principal Source of Circulating RBP4 in Mice.

Author information

1
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.
2
George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT.
3
Department of Medicine and Institute of Human Nutrition, Columbia University College of Physicians and Surgeons, New York, NY.
4
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.
5
Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
6
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.

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.

PMID:
27797907
PMCID:
PMC5204311
DOI:
10.2337/db16-0286
[Indexed for MEDLINE]
Free PMC Article

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