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09.09.2016 | Article

The suppression of hepatic glucose production improves metabolism and insulin sensitivity in subcutaneous adipose tissue in mice

verfasst von: Sylvie Casteras, Aya Abdul-Wahed, Maud Soty, Fanny Vulin, Hervé Guillou, Mélanie Campana, Hervé Le Stunff, Luciano Pirola, Fabienne Rajas, Gilles Mithieux, Amandine Gautier-Stein

Erschienen in: Diabetologia | Ausgabe 12/2016

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Abstract

Aims/hypothesis

Despite the strong correlation between non-alcoholic fatty liver disease and insulin resistance, hepatic steatosis is associated with greater whole-body insulin sensitivity in several models. We previously reported that the inhibition of hepatic glucose production (HGP) protects against the development of obesity and diabetes despite severe steatosis, thanks to the secretion of specific hepatokines such as fibroblast growth factor 21 (FGF21) and angiopoietin-related growth factor. In this work, we focused on adipose tissue to assess whether liver metabolic fluxes might, by interorgan communication, control insulin signalling in lean animals.

Methods

Insulin signalling was studied in the adipose tissue of mice lacking the catalytic subunit of glucose 6-phosphatase, the key enzyme in endogenous glucose production, in the liver (L-G6pc ^−/− mice). Morphological and metabolic changes in the adipose tissues were characterised by histological analyses, gene expression and protein content.

Results

Mice lacking HGP exhibited improved insulin sensitivity of the phosphoinositide 3-kinase/Akt pathway in the subcutaneous adipose tissue associated with a browning of adipocytes. The suppression of HGP increased FGF21 levels in lean animals, and increased FGF21 was responsible for the metabolic changes in the subcutaneous adipose tissue but not for its greater insulin sensitivity. The latter might be linked to an increase in the ratio of monounsaturated to saturated fatty acids released by the liver.

Conclusions

Our work provides evidence that HGP controls subcutaneous adipose tissue browning and insulin sensitivity through two pathways: the release of beneficial hepatokines and changes in hepatic fatty acids profile.

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Titel: The suppression of hepatic glucose production improves metabolism and insulin sensitivity in subcutaneous adipose tissue in mice
verfasst von: Sylvie Casteras
Aya Abdul-Wahed
Maud Soty
Fanny Vulin
Hervé Guillou
Mélanie Campana
Hervé Le Stunff
Luciano Pirola
Fabienne Rajas
Gilles Mithieux
Amandine Gautier-Stein
Publikationsdatum: 09.09.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 12/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4097-y

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The suppression of hepatic glucose production improves metabolism and insulin sensitivity in subcutaneous adipose tissue in mice

Abstract

Aims/hypothesis

Methods

Results

Conclusions

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Abstract

Aims/hypothesis

Methods

Results

Conclusions

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