TY  - JOUR
A1  - Fedders, Ronja
A1  - Muenzner, Matthias
A1  - Weber, Pamela
A1  - Sommerfeld, Manuela
A1  - Knauer, Miriam
A1  - Kedziora, Sarah
A1  - Kast, Naomi
A1  - Heidenreich, Steffi
A1  - Raila, Jens
A1  - Weger, Stefan
A1  - Henze, Andrea
A1  - Schupp, Michael
T1  - Liver-secreted RBP4 does not impair glucose homeostasis in mice
JF  - The journal of biological chemistry
N2  - Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.
KW  - liver
KW  - retinoid-binding protein
KW  - glucose metabolism
KW  - insulin resistance
KW  - mouse
KW  - TTR
Y1  - 2018
U6  - https://doi.org/10.1074/jbc.RA118.004294
SN  - 1083-351X
VL  - 293
IS  - 39
SP  - 15269
EP  - 15276
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  -