title: Metabolic abnormalities induced by mitochondrial dysfunction in skeletal muscle of the renal carcinoma Eker (TSC2+/-) rat model.
abstract: Tuberous sclerosis complex 2 (TSC2) is a mediator of insulin signal transduction, and a loss of function in TSC2 induces hyperactivation of mTORC1 pathway, which leads to tumorigenesis. We have previously demonstrated that Eker rat model, which is heterozygous for a TSC2 mutation, exhibits hyperglycemia and hyperketonemia. The present study was to investigate whether these changes also can affect metabolism in skeletal muscle of the Eker rat. Wild-type (TSC2+/+) and Eker (TSC2+/-) rats underwent an oral glucose tolerance test, and the latter showed decrease in whole-body glucose utilization. Additionally, reductions in the expression of glycolysis-, lipolysis-, and ketone body-related genes in skeletal muscle were observed in Eker rats. Furthermore, ATP content and mitochondrial DNA copy number were lower in skeletal muscle of Eker rats. These data demonstrate that heterozygous to mutation TSC2 not only affects the liver metabolism, but also skeletal muscle metabolism, via mitochondrial dysfunction.
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aizawa
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shirai
authors.affiliation: b Faculty of Medicine, Department of Pathology and Oncology , Juntendo University , Tokyo , Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: b Faculty of Medicine, Department of Pathology and Oncology , Juntendo University , Tokyo , Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tsujii
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Inoue
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Kazami
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Tadokoro
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: a Faculty of Applied Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006943:Hyperglycemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D007328:Insulin; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
keywords: Eker rat; TSC2; energy metabolism; mitochondrial dysfunction; skeletal muscle