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Diabetologia
Published in: Diabetologia 8/2016

01-08-2016 | Article

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

Authors: Edson M. de Oliveira, Thais P. Ascar, Jacqueline C. Silva, Silvana Sandri, Silene Migliorini, Ricardo A. Fock, Ana Campa

Published in: Diabetologia | Issue 8/2016

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Abstract

Aims/hypothesis

Pre-adipocytes and adipocytes are responsive to the acute phase protein serum amyloid A (SAA). The combined effects triggered by SAA encompass an increase in pre-adipocyte proliferation, an induction of TNF-α and IL-6 release and a decrease in glucose uptake in mature adipocytes, strongly supporting a role for SAA in obesity and related comorbidities. This study addressed whether SAA depletion modulates weight gain and insulin resistance induced by a high-fat diet (HFD).

Methods

Male Swiss Webster mice were fed an HFD for 10 weeks under an SAA-targeted antisense oligonucleotide (ASOSAA) treatment in order to evaluate the role of SAA in weight gain.

Results

With ASOSAA treatment, mice receiving an HFD did not differ in energy intake when compared with their controls, but were prevented from gaining weight and developing insulin resistance. The phenotype was characterised by a lack of adipose tissue expansion, with low accumulation of epididymal, retroperitoneal and subcutaneous fat content and decreased inflammatory markers, such as SAA3 and toll-like receptor (TLR)-4 expression, as well as macrophage infiltration into the adipose tissue. Furthermore, a metabolic status similar to chow-fed mice counterparts could be observed, with equivalent levels of leptin, adiponectin, IGF-I, SAA, fasting glucose and insulin, and remarkable improvement in glucose and insulin tolerance test profiles. Surprisingly, the expected HFD-induced metabolic endotoxaemia was also prevented by the ASOSAA treatment.

Conclusions/interpretation

This study provides further evidence of the role of SAA in weight gain and insulin resistance. Moreover, we also suggest that beyond its proliferative and inflammatory effects, SAA is part of the lipopolysaccharide signalling pathway that links inflammation to obesity and insulin resistance.
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Metadata
Title
Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice
Authors
Edson M. de Oliveira
Thais P. Ascar
Jacqueline C. Silva
Silvana Sandri
Silene Migliorini
Ricardo A. Fock
Ana Campa
Publication date
01-08-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 8/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-016-3970-z

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