Lipopolysaccharides (LPSs) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists, such as Escherichia coli-derived LPS. LPSs from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by endotoxin units (EUs). We found that E. coli LPS impairs gut barrier function and worsens glycemic control in mice, but equal doses of LPSs from other bacteria do not. Matching the LPS dose from R. sphaeroides and E. coli by EUs reveals that only E. coli LPS promotes dysglycemia and adipose inflammation, delays intestinal glucose absorption, and augments insulin and glucagon-like peptide (GLP)-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracts dysglycemia caused by an equal dose of E. coli LPS and improves glucose control in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load to include LPS characteristics, such as lipid A acylation, which dictates the effect of metabolic endotoxemia.

脂多糖 (LPS) 可以促进代谢性内毒素血症，这被认为是炎症和代谢有害的，基于 Toll 样受体 (TLR) 4 激动剂，例如大肠杆菌衍生的 LPS。来自某些细菌的 LPS 可拮抗 TLR4，但会导致通过内毒素单位 (EU) 测量的内毒素血症。我们发现大肠杆菌LPS 会损害肠道屏障功能并恶化小鼠的血糖控制，但来自其他细菌的等剂量 LPS 则不会。EUs 匹配来自R. sphaeroides和E. coli的 LPS 剂量表明，只有E. coliLPS 促进血糖异常和脂肪炎症，延缓肠道葡萄糖吸收，并增加胰岛素和胰高血糖素样肽 (GLP)-1 分泌。R. sphaeroides LPS促进的代谢有益的内毒素血症可抵消由等剂量的大肠杆菌LPS 引起的血糖异常，并改善肥胖小鼠的血糖控制。代谢性内毒素血症的概念应扩展到 LPS 负荷之外，包括 LPS 特征，例如脂质 A 酰化，这决定了代谢性内毒素血症的影响。