Elevated numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL) predict diabetes risk by unclear mechanisms. Upregulation of the innate immunity pathway, the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system, in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that LDL stimulate WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for risk factors for T2D related to systemic and WAT glucose and fat metabolism before and after 12-week supplementation with omega-3 fatty acids. Regulation of the NLRP3 inflammasome was explored in hip WAT biopsies and macrophages using LDL without/with the inflammasome priming and activation controls (LPS and ATP). Baseline data indicate that LDL induce IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and primary macrophages. Subjects with high-apoB (above median) had higher WAT IL-1β-secretion than subjects with low-apoB independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in subjects with high-apoB only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, LDL are priming signals of the human WAT NLRP3 inflammasome/IL-1β pathway. Targeting IL-1β in subjects with high-apoB may prevent T2D.