|CHUNG, EUNHEE - University Of Texas At San Antonio
|ELMASSRY, MOAMEN - Texas Tech University
|KAUR, GURVINDER - Texas Tech University Health Science Center
|DUFOUR, JANNETTE - Texas Tech University Health Science Center
|HAMOOD, ABDUL - Texas Tech University Health Science Center
|CHWAN-LI, SHEN - Texas Tech University Health Science Center
Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2021
Publication Date: 7/9/2021
Citation: Chung, E., Elmassry, M., Cao, J.J., Kaur, G., Dufour, J., Hamood, A., Chwan-Li, S. 2021. Beneficial effect of dietary geranylgeraniol on glucose homeostasis and bone microstructure in obese mice is associated with suppression of proinflammation and modification of gut microbiome. Journal of Agricultural and Food Chemistry. 93:27-37. https://doi.org/10.1016/j.nutres.2021.07.001.
Interpretive Summary: Studies show gut microbes affect type 2 diabetes mellitus, T2DM development and bone metabolism. It is well-known that many natural products and their bioactive compounds can reduce high blood sugar levels in T2DM and improve bone health. In this study, we tested if geranylgeraniol, a bioactive compound found in fruits and vegetables, supplemented in the diet of obese mice improved blood sugar and bone outcomes and evaluated if geranylgeraniol changed the composition of gut microbes. We found that geranylgeraniol supplementation reduced blood sugar levels based on glucose tolerance and insulin tolerance tests. geranylgeraniol increased levels of serum bone formation markers and decreased levels of serum bone resorption markers, indicating that geranylgeraniol benefits bone. geranylgeraniol reduced inflammation and changed the composition of the gut microbes. Our results demonstrate that geranylgeraniol improves outcomes related to T2DM and bone health in obese mice likely by changing the gut microbe composition and function.
Technical Abstract: This study examined the effects of dietary geranylgeraniol on glucose homeostasis, bone microstructure, cytokines, and gut microbiome in mice with 3 groups, low-fat diet, high-fat diet, and high-fat diet + geranylgeraniol at 800mg/kg diet for 14 weeks. Glucose homeostasis was assessed via serum and pancreas insulin levels and glucose and insulin tolerance tests. Bone microarchitecture was measured by micro-CT. The fecal microbiome was assessed by 16S rRNA sequencing. Serum monocyte chemoattractant protein-1 and interleukin-6 were measured. geranylgeraniol supplementation increased serum procollagen 1 intact N-terminal propeptide, stiffness at the femur and lumbar vertebrae-4, and cortical thickness at femoral midshaft, while decreasing serum collagen type 1 cross-linked C-telopeptide; improved glucose tolerance and insulin sensitivity; reduced serum monocyte chemoattractant protein-1 and interleukin-6; and increased abundance of Butyricicoccus pullicaecorum and decreased Dorea longicatena in the cecal microbiome. Collectively, geranylgeraniol improves glucose homeostasis and bone microstructure in obese mice, probably via suppression of pro-inflammation and modification of microbiome composition.