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 remain intact in LRKO mice, and increase as expected in the setting of diet-induced insulin-resistance. However, circulating RBP4 is 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 may therefore play a more important autocrine or paracrine function confined within the adipose tissue compartment.
* Both authors contributed equally to this work.
- Received February 29, 2016.
- Accepted October 14, 2016.
- © 2016 by the American Diabetes Association.