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Diabetologia

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Open Access 01-06-2016 | Article

Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition

Authors: Malgorzata S. Martin-Gronert, Denise S. Fernandez-Twinn, Martin Bushell, Kenneth Siddle, Susan E. Ozanne

Published in: Diabetologia | Issue 6/2016

Abstract

Aims/hypothesis

Individuals with a low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. This is associated with peripheral insulin resistance. Here, we aimed to determine whether changes in insulin signalling proteins in white adipose tissue (WAT) can be detected prior to the onset of impaired glucose tolerance, determine whether these changes are cell-autonomous and identify the underlying mechanisms involved.

Methods

Fourteen-month-old male rat offspring born to dams fed a standard protein (20%) diet or a low (8%) protein diet throughout gestation and lactation were studied. Fat distribution and adipocyte size were determined. Protein content and mRNA expression of key insulin signalling molecules were analysed in epididymal WAT and in pre-adipocytes that had undergone in vitro differentiation.

Results

The offspring of low protein fed dams (LP offspring) had reduced visceral WAT mass, altered fat distribution and a higher percentage of small adipocytes in epididymal WAT. This was associated with reduced levels of IRS1, PI3K p110β, Akt1 and PKCζ proteins and of phospho-Akt Ser473. Corresponding mRNA transcript levels were unchanged. Similarly, in vitro differentiated adipocytes from LP offspring showed reduced protein levels of IRβ, IRS1, PI3K p85α and p110β subunits, and Akt1. Levels of Akt Ser473 and IRS1 Tyr612 phosphorylation were reduced, while IRS1 Ser307 phosphorylation was increased.

Conclusions/interpretation

Maternal protein restriction during gestation and lactation changes the distribution and morphology of WAT and reduces the levels of key insulin signalling proteins in the male offspring. This phenotype is retained in in vitro differentiated adipocytes, suggesting that programming occurs via cell-autonomous mechanism(s).

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Title: Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition
Authors: Malgorzata S. Martin-Gronert
Denise S. Fernandez-Twinn
Martin Bushell
Kenneth Siddle
Susan E. Ozanne
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 6/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-3905-8

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