ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2023; 19(6):1713-1730. doi:10.7150/ijbs.82178 This issue Cite
Research Paper
BAP31 depletion inhibited adipogenesis, repressed lipolysis and promoted lipid droplets abnormal growth via attenuating Perilipin1 proteasomal degradation
1. Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, Liaoning, China
2. Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, Liaoning, China
3. School of Public Health, China Medical University, Shenyang, 110122, Liaoning, China
4. Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command of the Chinese People's Liberation Army, Shenyang, 110016, Liaoning, China
5. College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, 110819, Liaoning, China
6. Department of Electrical and Computer Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA
# These authors contributed equally to this work
Abstract
BAP31 expression was robustly decreased in obese white adipose tissue (WAT). To investigate the roles of BAP31 in lipid metabolism, adipocyte-specific conditional knockout mice (BAP31-ASKO) were generated. BAP31-ASKO mice grow normally as controls, but exhibited reduced lipid accumulation in WAT. Histomorphometric analysis reported increased adipocyte size in BAP31-ASKO mice. Mouse embryonic fibroblasts (MEFs) were induced to differentiation to adipocytes, showed reduced induction of adipogenic markers and attenuated adipogenesis in BAP31-deficient MEFs. BAP31-deficiency inhibited fasting-induced PKA signaling activation and the fasting response. β3-adrenergic receptor agonist-induced lipolysis also was reduced, accompanied by reduced free-fatty acids and glycerol release, and impaired agonist-induced lipolysis from primary adipocytes and adipose explants. BAP31 interacts with Perilipin1 via C-terminal cytoplasmic portion on lipid droplets (LDs) surface. Depletion of BAP31 repressed Perilipin1 proteasomal degradation, enhanced Perilipin1 expression and blocked LDs degradation, which promoted LDs abnormal growth and supersized LDs formation, resulted in adipocyte expansion, thus impaired insulin signaling and aggravated pro-inflammation in WAT. BAP31-deficiency increased phosphatidylcholine/phosphatidylethanolamine ratio, long chain triglycerides and most phospholipids contents. Overall, BAP31-deficiency inhibited adipogenesis and lipid accumulation in WAT, decreased LDs degradation and promoted LDs abnormal growth, pointing the critical roles in modulating LDs dynamics and homeostasis via proteasomal degradation system in adipocytes.
Keywords: BAP31, Perilipin1, Lipid droplet, Lipolysis, Proteasomal degradation
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