Maternal obesity in pregnancy developmentally programs adipose tissue inflammation in young, lean male mice offspring

Alfaradhi, M. Z., Kusinski, L. C., Fernandez-Twinn, D. S., Pantaleão, L. C., Carr, S. K., Ferland-McCollough, D., Yeo, G. S. H., Bushell, M. and Ozanne, S. E. (2016) Maternal obesity in pregnancy developmentally programs adipose tissue inflammation in young, lean male mice offspring. Endocrinology, 157(11), pp. 4246-4256. (doi: 10.1210/en.2016-1314) (PMID:27583789) (PMCID:PMC5086532)

Abstract

Obesity during pregnancy has a long-term effect on the health of the offspring including risk of developing the metabolic syndrome. Using a mouse model of maternal diet-induced obesity, we employed a genome-wide approach to investigate the microRNA (miRNA) and miRNA transcription profile in adipose tissue to understand mechanisms through which this occurs. Male offspring of diet-induced obese mothers, fed a control diet from weaning, showed no differences in body weight or adiposity at 8 weeks of age. However, offspring from the obese dams had up-regulated cytokine (Tnfα; P < .05) and chemokine (Ccl2 and Ccl7; P < .05) signaling in their adipose tissue. This was accompanied by reduced expression of miR-706, which we showed can directly regulate translation of the inflammatory proteins IL-33 (41% up-regulated; P < .05) and calcium/calmodulin-dependent protein kinase 1D (30% up-regulated; P < .01). We conclude that exposure to obesity during development primes an inflammatory environment in adipose tissue that is independent of offspring adiposity. Programming of adipose tissue miRNAs that regulate expression of inflammatory signaling molecules may be a contributing mechanism.

• Item Type: Articles
• Additional Information: This work was supported by the National Council for the Improvement of Higher Education Grant CAPES–Brazil–BEX 10594/13-2; the National Counsel of Technological and Scientific Development Grant CNPq–Brazil–PDE/204416/2014-0 (to L.C.P.); the Medical Research Council Grants MC UU 12012/4 and MC UU12012/5; the Biotechnologu and Biological Sciences Research Council Grant BB/M001636/1; and the Wellcome Trust Grant 089940/Z/09/Z.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bushell, Professor Martin
• Authors: Alfaradhi, M. Z., Kusinski, L. C., Fernandez-Twinn, D. S., Pantaleão, L. C., Carr, S. K., Ferland-McCollough, D., Yeo, G. S. H., Bushell, M., and Ozanne, S. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Endocrinology
• Publisher: Oxford University Press
• ISSN: 0013-7227
• ISSN (Online): 1945-7170
• Published Online: 01 September 2016
• Copyright Holders: Copyright © 2016 Endocrine Society
• First Published: First published in Endocrinology 157(11): 4246-4256
• Publisher Policy: Reproduced under a Creative Commons License