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Endocrinology. 2015 Oct;156(10):3528-37. doi: 10.1210/en.2015-1424. Epub 2015 Jul 27.

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.

Author information

1
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.

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.

PMID:
26214037
PMCID:
PMC4869840
DOI:
10.1210/en.2015-1424
[Indexed for MEDLINE]
Free PMC Article

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