Macrophage tumor necrosis factor-alpha deletion does not protect against obesity-associated metabolic dysfunction

The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been suggested to be a key factor in the induction of obesity-associated metabolic dysfunction. However, the role that macrophage-derived TNF-alpha has on regulating metabolic perturbations in obesity is not completely understood. Therefore, we utilized the TNF-alpha(Flox/Flox) ((F/F)), LyzMcre(+/-) mouse model to determine the impact that macrophage TNF-alpha deletion has on the development of high-fat diet (HFD)-induced obesity. At 10 weeks of age, male littermates were randomly assigned to 1 of 4 groups: TNF-alpha(F/F) low-fat diet (TNF-alpha(F/F) LFD), TNF-alpha(F/F,) (LyzMCre) LFD, TNF-alpha(F/F) HFD, or TNF-alpha(F/F,) (LyzMCre) HFD (n = 16-28/group) and were fed their respective diets for 18 weeks. Body weight was assessed throughout the course of the experiment. Body composition, hepatic lipid accumulation, and metabolic outcomes were also examined. A microarray gene expression experiment was performed from RNA isolated from epididymal adipose tissue of the HFD-fed groups (n = 10/group) and results were verified via qRT-PCR for all groups. Macrophage-derived TNF-alpha deletion significantly reduced adipose tissue TNF-alpha gene expression and circulating TNF-alpha and downregulated genes linked to the toll-like receptor (TLR) and NF kappa B signaling pathways. However, macrophage TNF-alpha deletion had no effect on hindering the development of obesity, hepatic lipid accumulation, or improving glucose metabolism or insulin sensitivity. In conclusion, macrophage-derived TNF-alpha is not a causative factor for the induction of obesity-associated metabolic dysfunction.

Automated summary

Macrophage-derived TNF-alpha does not play a significant role in the development of obesity, but can reduce TNF-alpha gene expression and circulating levels in adipose tissue, as well as modulate specific signaling pathway gene expression.