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

Author(s)

de Oliveira, Edson M. ^[1] ; Ascar, Thais P. ^[1] ; Silva, Jacqueline C. ^[1] ; Sandri, Silvana ^[1] ; Migliorini, Silene ^[1] ; Fock, Ricardo A. ^[1] ; Campa, Ana ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, 580 Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Diabetologia; v. 59, n. 8, p. 1760-1768, AUG 2016.
• Web of Science Citations: 5

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-alpha 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 (ASO(SAA)) treatment in order to evaluate the role of SAA in weight gain. Results With ASO(SAA) 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 ASO(SAA) 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. (AU)

• FAPESP's process: 10/18498-7 - New insights into the role of serum amyloid A (SAA) on obesity and insulin resistance
• Grantee: Edson Mendes de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/24052-4 - Acute inflammation in the genesis of obesity: experimental model focused on the protein serum amyloid a (SAA) as an adipose tissue marker of inflammation and hypertrophy
• Grantee: Ana Campa
• Support Opportunities: Regular Research Grants