Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice.
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.
Shelley
Piran
P
Division of Reproduction and Endocrinology, King's College London, St. Thomas's Hospital, London, UK.
Martin-Gronert
Malgorzata S
MS
Rowlerson
Anthea
A
Poston
Lucilla
L
Heales
S J R
SJ
Hargreaves
Iain P
IP
McConnell
Josie M
JM
Ozanne
Susan E
SE
Fernandez-Twinn
Denise S
DS
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001835:Body Weight; D058534:Class I Phosphatidylinositol 3-Kinases; D004195:Disease Models, Animal; D042963:Electron Transport Complex II / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000378:metabolism*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction; D014451:Ubiquinone / Q000378:metabolism; D000099221:Protein Kinase C zeta
D058534:Class I Phosphatidylinositol 3-Kinases; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D014451:Ubiquinone; D000099221:Protein Kinase C zeta; C526295:Irs1 protein, mouse; C495693:Slc2a4 protein, mouse; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; C030571:ubiquinone 9