Serum amyloid A3 is required for normal weight and immunometabolic function in mice

• DOI: 10.1371/journal.pone.0192352
• Publication Date: 2018-02-01T18:43:31Z
• Authors: Jennifer L. Ather; Matthew E. Poynter
• Keywords: Knockout mouse

Serum amyloid A (SAA) is an apolipoprotein that robustly upregulated in numerous inflammatory diseases and has been implicated as a candidate pro-inflammatory mediator. However, studies comparing endogenous SAAs recombinant forms of the acute phase protein have generated conflicting data on function SAA immunity. We SAA3 knockout mice to evaluate contribution immune-mediated disease, found lacking develop adult-onset obesity metabolic dysfunction along with defects innate immune development. Mice lack gain more weight, exhibit increased visceral adipose deposition, hepatic steatosis compared wild-type littermates. Leukocytes from tissue SAA3-/- express phenotype, bone marrow derived dendritic cells secrete levels IL-1β, IL-6, IL-23, TNFα response LPS mice. Finally, BMDC demonstrate impaired endotoxin tolerance inhibited responses retinoic acid. Our findings indicate modulates homeostasis.