Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity Journal Article
| Authors: | Shabrova, E.; Hoyos, B.; Vinogradov, V.; Kim, Y. K.; Wassef, L.; Leitges, M.; Quadro, L.; Hammerling, U. |
| Article Title: | Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity |
| Abstract: | We previously defined that the mitochondrialocalized PKCδ 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 PKCδ signalosome. Here, we tested in vivo if a persistent oversupply of retinol would further impair glucose metabolism in a mouse model of dietinduced insulin resistance. We crossed mice overexpressing human retinol-binding protein (hRBP) under the muscle creatine kinase (MCK) promoter (MCKhRBP) with the PKCδ-/- strain to generate mice with a different status of the PKCd signalosome and retinoid levels. Mice with a functional PKCδ signalosome and elevated retinoid levels (PKCδ+/+hRBP) developed the most advanced stage of insulinresistance. In contrast, elevationof retinoid levels in mice with inactivePKCδ did not affect remarkably their metabolism, resulting in phenotypic similarity between PKCδ-/-RBP and PKCδ-/- mice. Therefore, in addition to the well-defined role of PKCδ in the etiology of metabolic syndrome, we present a novel PKCδ signaling pathway that requires retinol as ametabolic cofactor and is involved in the regulation of fuel utilization in mitochondria. The distinct role in whole-body energy homeostasis establishes the PKCδ signalosome as a promising target for therapeutic intervention in metabolic disorders. © 2016 FASEB. |
| Keywords: | metabolic syndrome; vitamin a; pkcδ signalosome |
| Journal Title: | FASEB Journal |
| Volume: | 30 |
| Issue: | 3 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2016-03-01 |
| Start Page: | 1339 |
| End Page: | 1355 |
| Language: | English |
| DOI: | 10.1096/fj.15-281543 |
| PROVIDER: | scopus |
| PMCID: | PMC4750423 |
| PUBMED: | 26671999 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2016 -- Source: Scopus |
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