High Fat Diet Triggers a Prompt and Transient Increase in Adipose Tissue Granulocyte Colony Stimulating Factor and Circulating Myeloid Cells in Mice

Abstract

Scope: The short-term effects of feeding high fat diet (HFD) to mice was investigated with focus on the effect on myelopoesis, circulating neutrophils and the induction of Granulocyte colony stimulating factor (G-CSF). Methods: Male mice were fed HFD (45%) during a period of 5 weeks with samples taken after 3 days and 1, 3, 4 and 5 weeks. Blood was analyzed for neutrophils and monocytes, for G-CSF and granulocyte-macrophage (GM)-CSF, and for cytokine expression. Visceral adipose tissue (VAT) expression of various genes and production of G-GSF and GM-CSF in cultured VAT was determined. Results: Three days after commencement of HFD, the number of circulatory neutrophils and monocytes increased but returned to baseline-level at day 8. This transient increase coincided with an increased blood concentration of G-CSF and a transient increase in bone marrow and spleen neutrophils. In supernatant from cultivated visceral adipose tissue isolated from HFD fed mice on day 3 and 8, G-CSF was increased. The expression of Toll-like receptor 4 in adipose tissue was down-regulated from week 4. In vitro, lipopolysaccharide (LPS) was a poor stimulator of G-CSF, while G-CSF or LPS together with G-CSF or GM-CSF induced increased G-CSF production. G-CSF suppressed production of LPS-induced TNFa and increased IL-10 production in dendritic cells suggesting that G-CSF down-regulates LPS-induced inflammation. Conclusion: HFD induces a transient increase in adipose tissue G-GSF and circulating myeloid cells in mice. We suggest G-CSF induces increased myelopoiesis and simultaneously down-regulates LPS-induced inflammation.