title: Coenzyme Q10 Prevents Insulin Signaling Dysregulation and Inflammation Prior to Development of Insulin Resistance in Male Offspring of a Rat Model of Poor Maternal Nutrition and Accelerated Postnatal Growth.
abstract: Low birth weight and rapid postnatal growth increases the risk of developing insulin resistance and type 2 diabetes in later life. However, underlying mechanisms and potential intervention strategies are poorly defined. Here we demonstrate that male Wistar rats exposed to a low-protein diet in utero that had a low birth weight but then underwent postnatal catch-up growth (recuperated offspring) had reductions in the insulin signaling proteins p110-β (13% ± 6% of controls [P < .001]) and insulin receptor substrate-1 (39% ± 10% of controls [P < .05]) in adipose tissue. These changes were not accompanied by any change in expression of the corresponding mRNAs, suggesting posttranscriptional regulation. Recuperated animals displayed evidence of a proinflammatory phenotype of their adipose tissue with increased IL-6 (139% ± 8% [P < .05]) and IL1-β (154% ± 16% [P < .05]) that may contribute to the insulin signaling protein dysregulation. Postweaning dietary supplementation of recuperated animals with coenzyme Q (CoQ10) (1 mg/kg of body weight per day) prevented the programmed reduction in insulin receptor substrate-1 and p110-β and the programmed increased in IL-6. These findings suggest that postweaning CoQ10 supplementation has antiinflammatory properties and can prevent programmed changes in insulin-signaling protein expression. We conclude that CoQ10 supplementation represents an attractive intervention strategy to prevent the development of insulin resistance that results from suboptimal in utero nutrition.
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Ralitsa
authors.initials: R
authors.lastname: Madsen
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chen
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Asha
authors.initials: A
authors.lastname: Carpenter
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Josie M
authors.initials: JM
authors.lastname: McConnell
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit (J.L.T.-A., D.S.F.-T., R.M., J.-H.C., A.C., J.M.M., S.E.O.), Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 OQQ, United Kingdom; and Neurometabolic Unit (I.P.H.), National Hospital, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006130:Growth Disorders / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000502:physiology
chemical_list: D007328:Insulin; D008055:Lipids; D035683:MicroRNAs; D014451:Ubiquinone; C024989:coenzyme Q10