Pregnancy and Smoothelin-like Protein 1 (SMTNL1) Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice
| Autor: | Robert C. Hickner, Donghai Zheng, Douglas H. Weitzel, Khaldon Bodoor, Thomas J. Ribar, Timothy A.J. Haystead, David R. Loiselle, Beáta Lontay, James E. deVente, Donald P. McDonnell, Rachid Safi, Adrienn Sipos |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Proteomics
medicine.medical_specialty medicine.drug_class Steroid hormone receptor Muscle Proteins Biology Biochemistry Mice Insulin resistance Oxygen Consumption Pregnancy Internal medicine Progesterone receptor medicine Animals Humans Elméleti orvostudományok Muscle Skeletal Molecular Biology Estrogen Receptor alpha Skeletal muscle Cell Biology Orvostudományok Glucose Tolerance Test medicine.disease Phosphoproteins Endocrinology medicine.anatomical_structure Metabolism Gene Expression Regulation Estrogen Smoothelin Female Insulin Resistance Receptors Progesterone Glycolysis Gene Deletion Hormone |
| Popis: | Pregnancy promotes physiological adaptations throughout the body, mediated by the female sex hormones progesterone and estrogen. Changes in the metabolic properties of skeletal muscle enable the female body to cope with the physiological challenges of pregnancy and may also be linked to the development of insulin resistance. We conducted global microarray, proteomic, and metabolic analyses to study the role of the progesterone receptor and its transcriptional regulator, smoothelin-like protein 1 (SMTNL1) in the adaptation of skeletal muscle to pregnancy. We demonstrate that pregnancy promotes fiber-type changes from an oxidative to glycolytic isoform in skeletal muscle. This phenomenon is regulated through an interaction between SMTNL1 and progesterone receptor, which alters the expression of contractile and metabolic proteins. smtnl1(-/-) mice are metabolically less efficient and show impaired glucose tolerance. Pregnancy antagonizes these effects by inducing metabolic activity and increasing glucose tolerance. Our results suggest that SMTNL1 has a role in mediating the actions of steroid hormones to promote fiber switching in skeletal muscle during pregnancy. Our findings also bear on the management of gestational diabetes that develops as a complication of pregnancy in ~4% of women. |
| Databáze: | OpenAIRE |
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