| First Author | Oppong AK | Year | 2020 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 319 |
| Issue | 1 | Pages | E117-E132 |
| PubMed ID | 32369418 | Mgi Jnum | J:296834 |
| Mgi Id | MGI:6469114 | Doi | 10.1152/ajpendo.00093.2020 |
| Citation | Oppong AK, et al. (2020) Reducing 14-3-3zeta expression influences adipocyte maturity and impairs function. Am J Physiol Endocrinol Metab 319(1):E117-E132 |
| abstractText | One of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL) are critical lipolytic enzymes, and their phosphorylation generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. Although we previously identified essential roles of the 14-3-3zeta isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on ATGL and HSL suggests that 14-3-3zeta could also influence mature adipocyte processes like lipolysis. Here we demonstrate that 14-3-3zeta is necessary for lipolysis in male mice and fully differentiated 3T3-L1 adipocytes, as depletion of 14-3-3zeta significantly impaired glycerol and free fatty acid (FFA) release. Unexpectedly, reducing 14-3-3zeta expression was found to significantly impact adipocyte maturity, as observed by reduced abundance of peroxisome proliferator-activated receptor (PPAR)gamma2 protein and expression of mature adipocyte genes and those associated with de novo triglyceride synthesis and lipolysis. The impact of 14-3-3zeta depletion on adipocyte maturity was further examined with untargeted lipidomics, which revealed that reductions in 14-3-3zeta abundance promoted the acquisition of a lipidomic signature that resembled undifferentiated preadipocytes. Collectively, these findings reveal a novel aspect of 14-3-3zeta in adipocytes, as reducing 14-3-3zeta was found to have a negative effect on adipocyte maturity and adipocyte-specific processes like lipolysis. |
