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
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Tarry-Adkins, J., Twinn, D., Madsen, R., Chen, J., Carpenter, A., Hargreaves, I., McConnell, J., & et al. (2015). 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. Endocrinology https://doi.org/10.1210/en.2015-1424
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<0.001) and IRS-1 [39 ± 10% of controls] (p<0.05) in adipose tissue. These changes were not accompanied by any change in expression of the corresponding mRNAs, suggesting post-transcriptional regulation. Recuperated animals displayed evidence of a pro-inflammatory phenotype of their adipose tissue with increased interleukin-6 (IL-6) [139 ± 8%], (p<0.05) and interleukin-1β (IL1-β) [154 ± 16%], (p<0.05) that may contribute to the insulin signaling protein dysregulation. Post-weaning dietary supplementation of recuperated animals with Coenzyme Q (CoQ10) (1mg/kg of body weight/day) prevented the programmed reduction in IRS-1 and p110-β and the programmed increased in IL-6. These findings suggest that post-weaning CoQ10 supplementation has anti-inflammatory 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.
This work was supported by The British Heart Foundation [PG/09/037/27387, FS/09/029/27902]; Medical Research Council [MC UU 12012/4] and Diabetes UK [12/0004508]. SEO is a member of the MRC Metabolic Diseases Unit. IPH is supported by the Department of Health’s NIHR Biomedical Research Centres funding scheme at UCLH/UCL.
British Heart Foundation (FS/09/029/27902)
British Heart Foundation (PG/09/037/27387)
Diabetes UK (12/0004508)
External DOI: https://doi.org/10.1210/en.2015-1424
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249176