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Diabetologia
Published in: Diabetologia 12/2016

Open Access 01-12-2016 | Article

A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice

Authors: Camille Attané, Marie-Line Peyot, Roxane Lussier, Pegah Poursharifi, Shangang Zhao, Dongwei Zhang, Johane Morin, Marco Pineda, Shupei Wang, Olivier Dumortier, Neil B. Ruderman, Grant A. Mitchell, Brigitte Simons, S. R. Murthy Madiraju, Erik Joly, Marc Prentki

Published in: Diabetologia | Issue 12/2016

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Abstract

Aims/hypothesis

To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions.

Methods

Atgl flox/flox mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT/+;Atgl flox/flox mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD.

Results

ND-fed male B-Atgl-KO mice showed decreased insulinaemia and glucose-induced insulin secretion (GSIS) in vivo. Changes in GSIS correlated with the islet content of long-chain saturated monoacylglycerol (MAG) species that have been proposed to be metabolic coupling factors for insulin secretion. Exogenous MAGs restored GSIS in B-Atgl-KO islets. B-Atgl-KO male mice fed an HFD showed reduced insulinaemia, glycaemia in the fasted and fed states and after glucose challenge, as well as enhanced insulin sensitivity. Moreover, decreased insulinaemia in B-Atgl-KO mice was associated with increased energy expenditure, and lipid metabolism in brown (BAT) and white (WAT) adipose tissues, leading to reduced fat mass and body weight.

Conclusions/interpretation

ATGL in beta cells regulates insulin secretion via the production of signalling MAGs. Decreased insulinaemia due to lowered GSIS protects B-Atgl-KO mice from diet-induced obesity, improves insulin sensitivity, increases lipid mobilisation from WAT and causes BAT activation. The results support the concept that fuel excess can drive obesity and diabetes via hyperinsulinaemia, and that an islet beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion.
Appendix
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Metadata
Title
A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice
Authors
Camille Attané
Marie-Line Peyot
Roxane Lussier
Pegah Poursharifi
Shangang Zhao
Dongwei Zhang
Johane Morin
Marco Pineda
Shupei Wang
Olivier Dumortier
Neil B. Ruderman
Grant A. Mitchell
Brigitte Simons
S. R. Murthy Madiraju
Erik Joly
Marc Prentki
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 12/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-4105-2

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