Deletion of Serum Amyloid A Increases Weight Gain in Mice

Background: The serum amyloid A (SAA) proteins are acute-phase reactants that mediates inflammation and metabolism. Here we investigated potential mechanistic links between the intestinal microbiota and SAA using two murine models.

Methods: In germ-free (GF) and conventional (CONV) mice, we assessed ileal and colonic SAA over time by RT-qPCR. Then we examined microbiota perturbation and microbiota-mediated phenotypic changes in the presence (WT) or absence of SAA (KO mice). WT and KO mice were either reared separately or co-housed post-weaning. Mice were switched from normal chow to high-fat diet at 8 weeks of life. Body weight was monitored weekly, and ileal gene expression was examined by RT-qPCR.

Results: GF and CONV mice expressed differential microbiota-dependent regulation of SAA isoforms in the ileum and colon. In the presence of microbes, ileal SAA expression significantly increased over time, with greater expression of SAA1, SAA2, and SAA3 than in GF mice at day 42. In the colon, this age-related induction and subsequent enhanced expression of SAA1 and SAA2 was observed in GF mice instead. SAA knockout led to significantly higher post-weaning body weight gain than in WT mice. By week 11, KO mice gained 21% more weight than WT mice. Cohousing diminished the weight difference between WT and KO mice. SAA KO mice showed significantly higher expression of ileal SOCS1, a gene associated with obesity and metabolic syndrome.

Conclusion: Our results suggest that SAA expression is highly sensitive to microbial composition in the ileum and colon. The increased body weight in SAA KO mice may be mediated through altered gut microbiota and impaired host metabolism, which requires further investigation.