| First Author | Shabrova E | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 3 | Pages | 1339-55 |
| PubMed ID | 26671999 | Mgi Jnum | J:230890 |
| Mgi Id | MGI:5766421 | Doi | 10.1096/fj.15-281543 |
| Citation | Shabrova E, et al. (2016) Retinol as a cofactor for PKCdelta-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. FASEB J 30(3):1339-55 |
| abstractText | We previously defined that the mitochondria-localized PKCdelta signaling complex stimulates the conversion of pyruvate to acetyl-coenzyme A by the pyruvate dehydrogenase complex. We demonstrated in vitro and ex vivo that retinol supplementation enhances ATP synthesis in the presence of the PKCdelta signalosome. Here, we tested in vivo if a persistent oversupply of retinol would further impair glucose metabolism in a mouse model of diet-induced insulin resistance. We crossed mice overexpressing human retinol-binding protein (hRBP) under the muscle creatine kinase (MCK) promoter (MCKhRBP) with the PKCdelta(-/-) strain to generate mice with a different status of the PKCdelta signalosome and retinoid levels. Mice with a functional PKCdelta signalosome and elevated retinoid levels (PKCdelta(+/+)hRBP) developed the most advanced stage of insulin resistance. In contrast, elevation of retinoid levels in mice with inactive PKCdelta did not affect remarkably their metabolism, resulting in phenotypic similarity between PKCdelta(-/-)hRBP and PKCdelta(-/-) mice. Therefore, in addition to the well-defined role of PKCdelta in the etiology of metabolic syndrome, we present a novel PKCdelta signaling pathway that requires retinol as a metabolic cofactor and is involved in the regulation of fuel utilization in mitochondria. The distinct role in whole-body energy homeostasis establishes the PKCdelta signalosome as a promising target for therapeutic intervention in metabolic disorders.-Shabrova, E., Hoyos, B., Vinogradov, V., Kim, Y.-K., Wassef, L., Leitges, M., Quadro, L., Hammerling, U. Retinol as a cofactor for PKCdelta-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity. |
