Document Detail


Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice.
MedLine Citation:
PMID:  19535678     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently reported insulin resistance in adult offspring of obese C57BL/6J mice. We have now evaluated whether parameters of skeletal muscle structure and function may play a role in insulin resistance in this model of developmental programming. Obesity was induced in female mice by feeding a highly palatable sugar and fat-rich diet for 6 wk prior to pregnancy, and during pregnancy and lactation. Offspring of obese dams were weaned onto standard laboratory chow. At 3 mo of age, skeletal muscle insulin signaling protein expression, mitochondrial electron transport chain activity (ETC), muscle fiber type, fiber density, and fiber cross-sectional area were compared with that of offspring of control dams weaned onto the chow diet. Female offspring of obese dams demonstrated decreased skeletal muscle expression of p110beta, the catalytic subunit of PI3K (P < 0.01), as well as reduced Akt phosphorylation at Serine residue 473 compared with control offspring. Male offspring of obese dams demonstrated increased skeletal muscle Akt2 and PKCzeta expression (P < 0.01; P < 0.001, respectively). A decrease in mitochondrial-linked complex II-III was observed in male offspring of obese dams (P < 0.01), which was unrelated to CoQ deficiency. This was not observed in females. There were no differences in muscle fiber density between offspring of obese dams and control offspring in either sex. Sex-related alterations in key insulin-signaling proteins and in mitochondrial ETC may contribute to a state of insulin resistance in offspring of obese mice.
Authors:
Piran Shelley; Malgorzata S Martin-Gronert; Anthea Rowlerson; Lucilla Poston; S J R Heales; Iain P Hargreaves; Josie M McConnell; Susan E Ozanne; Denise S Fernandez-Twinn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-17
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  297     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-25     Completed Date:  2009-09-10     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R675-81     Citation Subset:  IM    
Affiliation:
Division of Reproduction and Endocrinology, King's College London, St. Thomas's Hospital, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animal Nutritional Physiological Phenomena
Animals
Body Weight
Class I Phosphatidylinositol 3-Kinases
Disease Models, Animal
Electron Transport Complex II / metabolism*
Electron Transport Complex III / metabolism*
Female
Glucose Transporter Type 4 / metabolism
Insulin / metabolism*
Insulin Receptor Substrate Proteins / metabolism
Insulin Resistance*
Male
Maternal Nutritional Physiological Phenomena
Mice
Mice, Inbred C57BL
Mitochondria, Muscle / enzymology,  metabolism*
Muscle Fibers, Skeletal / metabolism
Obesity / metabolism*,  pathology,  physiopathology
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Pregnancy
Prenatal Exposure Delayed Effects
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Quadriceps Muscle / enzymology,  metabolism*,  pathology
Receptor, Insulin / metabolism
Sex Factors
Signal Transduction*
Ubiquinone / metabolism
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council; //British Heart Foundation
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 4; 0/Insulin; 0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, mouse; 0/Slc2a4 protein, mouse; 1339-63-5/Ubiquinone; 303-97-9/ubiquinone 9; EC 1.10.2.2/Electron Transport Complex III; EC 1.3.5.1/Electron Transport Complex II; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.137/1-phosphatidylinositol 3-kinase p110 subunit, mouse; EC 2.7.1.137/Class I Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, Insulin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/protein kinase C zeta; EC 2.7.11.13/Protein Kinase C
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