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01-02-2015 | Article

Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice

Authors: Farnaz Keyhani-Nejad, Martin Irmler, Frank Isken, Eva K. Wirth, Johannes Beckers, Andreas L. Birkenfeld, Andreas F. H. Pfeiffer

Published in: Diabetologia | Issue 2/2015

Abstract

Aims/hypothesis

High intake of carbohydrates, particularly sucrose, in western societies is associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related primarily to the carbohydrate quantity or to the hormonal responses, particularly glucose-dependent insulinotropic polypeptide (GIP), which is released in the proximal intestine. Therefore, we investigated the role of GIP by comparing two glucose–fructose dimers, sucrose and Palatinose (isomaltulose), resorbed proximally or distally.

Methods

The glycaemic and incretin responses to sucrose and Palatinose were studied by oral gavage and meal tests. We then analysed phenotypic and metabolic diet-induced changes in C57Bl/6J mice exposed to isoenergetic diets differing in carbohydrate type. Studies were repeated in GIP receptor knockout (Gipr ^−/−) mice and their wild-type littermates.

Results

Compared with sucrose, Palatinose intake resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks, Palatinose feeding prevented hepatic steatosis (48.5%) compared with sucrose and improved glucose tolerance, without differences in body composition and food intake. Ablation of GIP signalling in Gipr ^−/− mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased 2.3-fold the hepatic expression of Socs2, which is involved in the growth hormone signalling pathway and participates in the development of NAFL.

Conclusions/interpretation

Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of Socs2.

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Title: Nutritional strategy to prevent fatty liver and insulin resistance independent of obesity by reducing glucose-dependent insulinotropic polypeptide responses in mice
Authors: Farnaz Keyhani-Nejad
Martin Irmler
Frank Isken
Eva K. Wirth
Johannes Beckers
Andreas L. Birkenfeld
Andreas F. H. Pfeiffer
Publication date: 01-02-2015
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 2/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3423-5

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Methods

Results

Conclusions/interpretation

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