title: Pregnancy and Smoothelin-like Protein 1 (SMTNL1) Deletion Promote the Switching of Skeletal Muscle to a Glycolytic Phenotype in Human and Mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710; Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen-4032, Hungary.
authors.forename: Beata
authors.initials: B
authors.lastname: Lontay
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Khaldon
authors.initials: K
authors.lastname: Bodoor
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen-4032, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Sipos
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Weitzel
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: David
authors.initials: D
authors.lastname: Loiselle
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Rachid
authors.initials: R
authors.lastname: Safi
authors.affiliation: Departments of Kinesiology, East Carolina University, Greenville, North Carolina 27858.
authors.forename: Donghai
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, East Carolina University, Greenville, North Carolina 27834.
authors.forename: James
authors.initials: J
authors.lastname: Devente
authors.affiliation: Departments of Kinesiology, East Carolina University, Greenville, North Carolina 27858; Department of Biokinetics, Exercise, and Leisure Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hickner
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
authors.affiliation: Duke iPSC Shared Resource Facility, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ribar
authors.affiliation: Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710. Electronic address: timothy.haystead@duke.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Haystead
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006019:Glycolysis; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D040901:Proteomics; D011980:Receptors, Progesterone / Q000032:analysis / Q000378:metabolism; D000096985:Calponins
chemical_list: D047628:Estrogen Receptor alpha; D009124:Muscle Proteins; D010750:Phosphoproteins; D011980:Receptors, Progesterone; C543629:SMTNL1 protein, human; D000096985:Calponins; C491838:SMTNL1 protein, mouse; C097314:progesterone receptor B
keywords: gene expression; pregnancy; proteomics; skeletal muscle; smoothelin-like protein 1; steroid hormone receptor