Biliverdin Reductase A (BVRA) Knockout in Adipocytes Induces Hypertrophy and Reduces Mitochondria in White Fat of Obese Mice
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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) (BlvraFatKO) in mice to determine the function of BVRA in adipocytes and how it may impact adipose tissue expansion. The BlvraFatKO and littermate control (BlvraFlox) 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, BlvraFatKO mice had significantly higher visceral fat as compared to the BlvraFlox. 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 BlvraFatKO 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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Results regarding inhibitory effects of high-dose NAM were inconclusive in several animal studies.
“the results regarding the inhibitory effects of a high dose of NAM were inconclusive in several animal studies195.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [195]
High levels of methylated NAM have been associated with pathogenesis of type 2 diabetes, Parkinson disease and cardiac diseases.
“High levels of methylated NAM have been associated with the pathogenesis of type 2 diabetes, Parkinson disease and cardiac diseases195.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [195]
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References 79 · Cited by 50
- Authors
- Stec, D. E., Gordon, D. M., Nestor-Kalinoski, A. L., Donald, M. C., Mitchell, Z. L., Creeden, J. F., & Hinds, T. D.
- Affiliations
- University of Mississippi Medical Center (US)
- University of Toledo (US)
- Advanced Microscopy & Imaging Center, Department of Surgery, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
- Corresponding author
- Stec, David E.
- Hinds, Terry D.
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2020-03-02
- Volume
- 10
- Issue
- 3
- Pages
- 387
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7175174
- OpenAlex
- W3010016842
- Cited by
- 50
- References
- 79
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 10
- FWCI
- 5.57
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (K01HL-125445, L32MD009154, P01 HL05197-11, P20GM104357-02)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- biliverdin reductase A, adipocytes, white adipose tissue, adipocyte hypertrophy, mitochondrial number, beige adipocytes, adipose tissue browning, insulin signaling, insulin resistance, visceral fat, obesity, high-fat diet, adipose tissue inflammation, PPARα, beta3-adrenergic receptor, Akt phosphorylation, GLUT4
- MeSH terms
- Animals, Hypertrophy, Mitochondria, Obesity, Mice, Knockout, Receptors, Adrenergic, beta-3, Oxidoreductases Acting on CH-CH Group Donors, PPAR alpha, Mice, Adipose Tissue, White, Adipocytes, White, Gene Knockout Techniques
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