Serum amyloid A3 does not contribute to circulating SAA levels.

Area of Science:

• Biochemistry
• Immunology
• Metabolic Diseases

Background:

• Adipose tissue secretes serum amyloid A (SAA), a protein involved in inflammation.
• Elevated circulating SAA levels are observed in obese humans, but the origins and roles of adipose-derived SAA and hyperlipidemia remain unclear.
• Distinct SAA isoforms are produced by adipose tissue (SAA3) and the liver (SAA1 and 2) in mice.

Purpose of the Study:

• To investigate whether adipose tissue contributes to circulating SAA levels in obesity and hyperlipidemia.
• To differentiate the roles of adipose-derived SAA3 versus liver-derived SAA1/2 in obesity-associated inflammation.

Main Methods:

• Comparison of circulating SAA levels in genetically obese (ob/ob) mice and hyperlipidemic (Apoe(-/-)) mice versus their littermate controls.
• Quantitative analysis of SAA1/2 and SAA3 mRNA expression in liver and adipose tissue, respectively.
• Mass spectrometric analysis of SAA isoforms in high-density lipoprotein (HDL) from circulation and in conditioned medium from cultured adipocytes.

Main Results:

• Obese (ob/ob) mice exhibited significantly higher circulating SAA levels compared to controls, while hyperlipidemic (Apoe(-/-)) mice did not.
• Obesity significantly increased SAA1/2 mRNA in the liver and SAA3 mRNA in intra-abdominal fat.
• Hyperlipidemia did not affect SAA mRNA expression in either tissue.
• Circulating SAA detected in HDL consisted of SAA1/2 and SAA4, with no detectable SAA3.
• SAA3 was detected in the medium of cultured adipocytes, indicating secretion by these cells.

Conclusions:

• Adipose tissue expression of SAA3 is upregulated by obesity in mice.
• Despite increased expression, SAA3 secreted by adipose tissue does not contribute to the circulating SAA pool.
• Liver-derived SAA1/2 and SAA4 are the primary forms of SAA found in the circulation of obese mice.