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Am J Physiol Regul Integr Comp Physiol 297: R675-R681, 2009. First published June 17, 2009; doi:10.1152/ajpregu.00146.2009
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ARTICLES

Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice

Piran Shelley,1 Malgorzata S. Martin-Gronert,2 Anthea Rowlerson,3 Lucilla Poston,1 S. J. R. Heales,4 Iain P. Hargreaves,4 Josie M. McConnell,1 Susan E. Ozanne,2 and Denise S. Fernandez-Twinn2

1Division of Reproduction and Endocrinology, King's College London, St. Thomas's Hospital, London, UK; 2University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK; 3Applied Biomedical Research Group, King's College London, London, UK; and 4Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK

Submitted 10 March 2009 ; accepted in final form 10 June 2009

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 p110β, 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 PKC{zeta} 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.

maternal obesity; developmental programming; electron transport chain; insulin signaling; muscle metabolism


Address for reprint requests and other correspondence: Denise S. Fernandez-Twinn, Univ. of Cambridge Metabolic Research Labs., Institute of Metabolic Science, Level 4, Box 289, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 OQQ, UK (e-mail: df220{at}cam.ac.uk)






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