title: Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Edson M
authors.initials: EM
authors.lastname: de Oliveira
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Thais P
authors.initials: TP
authors.lastname: Ascar
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Silva
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Sandri
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Silene
authors.initials: S
authors.lastname: Migliorini
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Fock
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 580 Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil. anacampa@usp.br.
authors.forename: Ana
authors.initials: A
authors.lastname: Campa
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019446:Endotoxemia / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain / Q000235:genetics / Q000502:physiology*
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D000685:Serum Amyloid A Protein; D007334:Insulin-Like Growth Factor I
keywords: Adipocyte; CD14; Infection; Inflammation; SAA; SR-BI; TLR-2; TLR-4