Geranylgeraniol (GGOH) is found in edible oils such as olive, linseed, and sunflower oils, which have favorable metabolic effects. However, it is unknown whether these physiological benefits are mediated through the gut microbiome. Thus, the purpose of this study was to test the hypothesis that GGOH supplementation would improve glucose homeostasis and benefit the bone microstructure in obese mice through suppression of inflammation and modification of gut microbiota composition. Thirty-six male C57BL/6J mice were divided into 3 groups: a low-fat diet, a high-fat diet (HFD), and an HFD supplemented with 800 mg GGOH/kg diet (GG) for 14 weeks. Glucose and insulin tolerance tests were measured at baseline and end of study. The concentrations of adipokine cytokines (resistin, leptin, monocyte chemoattractant protein-1, interleukin-6) were measured via ELISA. Bone microarchitecture and quality were measured by micro-CT. Microbiome analysis was performed using 16S rRNA amplicon sequencing on cecal content. Relative to the HFD group, the GG group: (1) improved glucose tolerance and insulin sensitivity; (2) reduced production of pro-inflammatory adipokines, (3) increased serum procollagen I intact N-terminal propeptide (bone formation marker) concentrations, while decreasing serum collagen type 1 cross-linked C-telopeptide (bone resorption marker) levels, and (4) increased stiffness at both femur and LV-4 and cortical thickness at femoral midshaft. Compared to the HFD group, the GG group had an increased abundance of Butyricicoccus pullicaecorum and decreased Dorea longicatena in the cecal microbiome. Collectively, GGOH improves glucose homeostasis and bone microstructure in obese mice, probably via suppression of pro-inflammation and modification of microbiome composition.

香叶基香叶醇 (GGOH) 存在于橄榄油、亚麻籽和向日葵油等食用油中，具有良好的代谢作用。然而，尚不清楚这些生理益处是否是通过肠道微生物群介导的。因此，本研究的目的是验证补充 GGOH 可通过抑制炎症和改变肠道微生物群组成来改善肥胖小鼠的葡萄糖稳态并有益于骨骼微结构的假设。将 36 只雄性 C57BL/6J 小鼠分为 3 组：低脂饮食、高脂饮食 (HFD) 和补充 800 mg GGOH/kg 饮食 (GG) 的 HFD，持续 14 周。在基线和研究结束时测量葡萄糖和胰岛素耐量测试。脂肪因子细胞因子（抵抗素、瘦素、单核细胞趋化蛋白 1、白细胞介素-6）通过ELISA测量。通过显微CT测量骨微结构和质量。使用 16S rRNA 扩增子测序对盲肠内容物进行微生物组分析。相对于HFD组，GG组：（1）改善了糖耐量和胰岛素敏感性；(2) 减少促炎性脂肪因子的产生，(3) 增加血清前胶原 I 完整 N 端前肽（骨形成标志物）浓度，同时降低血清 1 型胶原交联 C 端肽（骨吸收标志物）水平，和(4) 增加股骨和 LV-4 的刚度以及股骨中轴的皮质厚度。与HFD组相比，GG组的丰度增加 使用 16S rRNA 扩增子测序对盲肠内容物进行微生物组分析。相对于HFD组，GG组：（1）改善了糖耐量和胰岛素敏感性；(2) 减少促炎性脂肪因子的产生，(3) 增加血清前胶原 I 完整 N 端前肽（骨形成标志物）浓度，同时降低血清 1 型胶原交联 C 端肽（骨吸收标志物）水平，和(4) 增加股骨和 LV-4 的刚度以及股骨中轴的皮质厚度。与HFD组相比，GG组的丰度增加 使用 16S rRNA 扩增子测序对盲肠内容物进行微生物组分析。相对于HFD组，GG组：（1）改善了糖耐量和胰岛素敏感性；(2) 减少促炎性脂肪因子的产生，(3) 增加血清前胶原 I 完整 N 端前肽（骨形成标志物）浓度，同时降低血清 1 型胶原交联 C 端肽（骨吸收标志物）水平，和(4) 增加股骨和 LV-4 的刚度以及股骨中轴的皮质厚度。与HFD组相比，GG组的丰度增加 (3) 增加血清前胶原 I 完整 N 端前肽（骨形成标志物）浓度，同时降低血清 1 型胶原交联 C 端肽（骨吸收标志物）水平，和 (4) 增加股骨和 LV- 的刚度4 股骨中段皮质厚度。与HFD组相比，GG组的丰度增加 (3) 增加血清前胶原 I 完整 N 端前肽（骨形成标志物）浓度，同时降低血清 1 型胶原交联 C 端肽（骨吸收标志物）水平，和 (4) 增加股骨和 LV- 的刚度4 股骨中段皮质厚度。与HFD组相比，GG组的丰度增加Butyricicoccus pullicaecorum和盲肠微生物组中的 Dorea longicatena 减少。总的来说，GGOH 可能通过抑制促炎症和改变微生物组组成来改善肥胖小鼠的葡萄糖稳态和骨骼微结构。