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Retinol Binding Protein 4 (RBP4) in Adipocytes and Obesity
Author(s) -
Shmarakov Igor,
Lee SeungAh,
Blaner William S.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.238.4
Subject(s) - medicine , endocrinology , brown adipose tissue , white adipose tissue , adipocyte , biology , adipose tissue , steatosis , triglyceride , cholesterol
We have earlier reported the generation and study of transgenic mice that express human RBP4 (hRBP4) in both white and brown adipocytes (Lee et al. Hepatology 2016, 64:1534–1546). Our published studies of these mice (adi‐hRBP4 mice) established that white adipocyte expression RBP4 induces inflammation in white adipose tissue (WAT) that is responsible for the hepatic steatosis phenotype seen in chow fed adi‐hRBP4 mice. When maintained on a high fat diet, adi‐hRBP4 mice gain significantly more body weight than matched control mice. We have investigated the basis for this weight gain phenotype and found that this involves marked RBP4‐induced changes in brown adipose tissue (BAT) physiology. H&E stained BAT obtained from adi‐hRBP4 mice shows the presence of large unilocular lipids in brown adipocytes. Biochemical measures establish that there is elevated triglyceride accumulation in BAT of adi‐hRBP4 mice that is accompanied by increased expression in BAT of genes involved in triglyceride synthesis. In addition, BAT from adi‐hRBP4 mice shows diminished expression levels for genes involved in BAT identity and function. Most importantly, uncoupling protein‐1 (UCP1) mRNA and protein levels are markedly reduced. This is accompanied by significantly diminished BAT levels of all‐ trans ‐retinoic acid. In vitro studies involving the use of mouse embryonic fibroblasts (MEFs) obtained from adi‐hRBP4 and matched control mice as well as brown and white stromal vascular cells induced to differentiate to adipocytes, confirmed that RBP4 expression in brown adipocytes alters gene expression patterns in the differentiated adipocytes. Collectively, our data suggest that elevated RBP4 expression in BAT effects all‐ trans ‐retinoic acid‐mediated processes giving rise to a whitening of BAT and diminished BAT actions. We propose that this underlies the weight gain phenotype we have observed. Support or Funding Information Supported by NIH grants R01 DK068437 and R01 DK101251 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .