Knockdown of TREM‐1 alleviates inflammation in HFD‐fed mice via regulating NF‐κB. qRT‐PCR analysis of TREM‐1 mRNA in HFD‐fed mice injected with supernatant in cell culture of shTREMs (Lv‐shTREMs) that knockdown of TREM‐1. Western blot analysis of TREM‐1 protein in HFD‐fed mice injected with supernatant in cell culture of shTREMs (Lv‐shTREMs) that knockdown of TREM‐1. The effect of NF‐κB inhibitor PDTC and Lv‐shTREMs on expression of p65 and p‐p65 in HFD‐fed mice was detected by Western blot analysis. qRT‐PCR analysis of IL‐1β, IL‐6, TNF‐α, IFN‐γ, MCP‐1 and MIP‐1α mRNA in HFD‐fed mice injected with Lv‐shTREMs that knockdown of TREM‐1. H&E staining analysis of the effect of NF‐κB inhibitor PDTC and Lv‐shTREMs on tissue morphology and architecture in HFD‐fed mice. *P < 0.05, **P < 0.01, and ***P < 0.001. GAPDH, glyceraldehyde 3‐phosphate dehydrogenase; HFD, high‐fat diet; H&E, hematoxylin and eosin; IFN‐γ, interferon‐γ; IL, interleukin; Lv, lentiviral vector; MCP‐1, monocyte chemoattractant protein‐1; MIP‐1α, macrophage inflammatory protein‐1α; mRNA, messenger RNA; PDTC, pyrrolidine dithiocarbamate; PMH, primary mouse hepatocytes; qRT‐PCR, quantitative reverse‐transcription polymerase chain reaction; shTREM, short hairpin RNAs of TREM‐1; TNF‐α, tumor necrosis factor‐α; TREM‐1, triggering receptor expressed on myeloid cells‐1