Journal
BIOMOLECULES
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/biom10030387
Keywords
obesity; WAT; BAT; adipose; brown fat; beige fat; bilirubin
Categories
Funding
- National Institutes of Health [L32MD009154]
- National Heart, Lung and Blood Institute [K01HL-125445, P01 HL05197-11]
- National Institute of General Medical Sciences [P20GM104357-02]
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Biliverdin reductase (BVR) is an enzymatic and signaling protein that has multifaceted roles in physiological systems. Despite the wealth of knowledge about BVR, no data exist regarding its actions in adipocytes. Here, we generated an adipose-specific deletion of biliverdin reductase-A (BVRA) (Blvra(FatKO)) in mice to determine the function of BVRA in adipocytes and how it may impact adipose tissue expansion. The Blvra(FatKO) and littermate control (Blvra(Flox)) mice were placed on a high-fat diet (HFD) for 12 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were quantitated at the end of the 12 weeks. The data showed that the percent body fat and body weights did not differ between the groups; however, Blvra(FatKO) mice had significantly higher visceral fat as compared to the Blvra(Flox). The loss of adipocyte BVRA decreased the mitochondrial number in white adipose tissue (WAT), and increased inflammation and adipocyte size, but this was not observed in brown adipose tissue (BAT). There were genes significantly reduced in WAT that induce the browning effect such as Ppara and Adrb3, indicating that BVRA improves mitochondria function and beige-type white adipocytes. The Blvra(FatKO) mice also had significantly higher fasting blood glucose levels and no changes in plasma insulin levels, which is indicative of decreased insulin signaling in WAT, as evidenced by reduced levels of phosphorylated AKT (pAKT) and Glut4 mRNA. These results demonstrate the essential role of BVRA in WAT in insulin signaling and adipocyte hypertrophy.
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