@article{FeddersMuenznerWeberetal.2021, author = {Fedders, Ronja and Muenzner, Matthias and Weber, Pamela and Sommerfeld, Manuela and Knauer, Miriam and Kedziora, Sarah and Kast, Naomi and Heidenreich, Steffi and Raila, Jens and Weger, Stefan and Henze, Andrea and Schupp, Michael}, title = {Liver-secreted RBP4 does not impair glucose homeostasis in mice}, series = {The journal of biological chemistry}, volume = {293}, journal = {The journal of biological chemistry}, number = {39}, publisher = {American Society for Biochemistry and Molecular Biology}, address = {Bethesda}, issn = {1083-351X}, doi = {10.1074/jbc.RA118.004294}, pages = {15269 -- 15276}, year = {2021}, abstract = {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.}, language = {en} } @article{FruscalzoFrommerLonderoetal.2017, author = {Fruscalzo, Arrigo and Frommer, Julia-Marie and Londero, Ambrogio P. and Henze, Andrea and Schweigert, Florian J. and Nofer, Jerzy-Roch and Steinhard, Johannes and Klockenbusch, Walter and Schmitz, Ralf and Raila, Jens}, title = {First trimester TTR-RBP4-ROH complex and angiogenic factors in the prediction of small for gestational age infant's outcome}, series = {Archives of gynecology and obstetrics}, volume = {295}, journal = {Archives of gynecology and obstetrics}, publisher = {Springer}, address = {Heidelberg}, issn = {0932-0067}, doi = {10.1007/s00404-017-4338-4}, pages = {1157 -- 1165}, year = {2017}, abstract = {To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10\%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3\% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95\% CI 1.40-1.75) vs 1.62 (95\% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95\% CI 32.3-66.3) vs 62.9 pg/ml (95\% CI 45.2-78.4) and 906 pg/ml (95\% CI 727-1626) vs 1610 pg/ml (95\% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses.}, language = {en} } @article{KwanbunjanPanprathipPhosatetal.2018, author = {Kwanbunjan, Karunee and Panprathip, Pornpimol and Phosat, Chanchira and Chumpathat, Noppanath and Wechjakwen, Naruemon and Puduang, Somchai and Auyyuenyong, Ratchada and Henkel, Ina and Schweigert, Florian J.}, title = {Association of retinol binding protein 4 and transthyretin with triglyceride levels and insulin resistance in rural thais with high type 2 diabetes risk}, series = {BMC Endocrine Disorders}, volume = {18}, journal = {BMC Endocrine Disorders}, publisher = {BMC}, address = {London}, issn = {1472-6823}, doi = {10.1186/s12902-018-0254-2}, pages = {7}, year = {2018}, abstract = {Background: Retinol binding protein 4 (RBP4), a protein secreted by adipocytes and bound in plasma to transthyretin (TTR), has been associated with obesity, the early phase of insulin resistance, metabolic syndrome, and type 2 diabetes mellitus. The objective of this study was to elucidate the relationship between RBP4, TTR, triglyceride (TG) and type 2 diabetes risk in rural Thailand. Results: RBP4 and TTR levels, as well as homeostatic model assessment of insulin resistance (HOMA-IR) values, were significantly elevated among subjects with high triglyceride levels (p < 0.01, p < 0.05, p < 0.05, respectively). Triglyceride levels correlated with RBP4 (r = 0.34, p < 0.001) and TTR (r= 0.26, p < 0.01) levels, as well as HOMA-IR values (r= 0.16, p < 0.05). After adjustment for age and gender, the risk of hypertriglyceridemia was 3.7 times greater (95\% Cl =1.42 -9.73, p = 0.008) in the highest RBP4 tertile as compared to the lowest tertile. Similarly, the highest TTR and HOMA-IR tertiles had greater risk of hypertriglyceridemia at 3.5 (95\% Cl = 1.30-9.20, p = 0.01) and 3.6 (95\% CI = 1.33- 9.58, p = 0.01) times higher than the respective lowest tertiles. The correlation between TTR and blood glucose was statistically significant (r 0.18, p < 0.05), but not found this relationship in RBP4. Conclusions: The associations of RBP4 and TTR with hypertriglyceridemia and insulin resistance may have important implications for the risk of heart disease and stroke.}, language = {en} }