Effect of dietary geranylgeraniol and green tea polyphenols on glucose homeostasis, bone turnover biomarkers, and bone microstructure in obese mice

Authors: SHEN, CHWAN-LI - Texas Tech University Health Science Center; DUFOUR, JANNETTE - Texas Tech University Health Science Center; MIRANDA, JONATHAN - Texas Tech University Health Science Center; KAUR, GURVINDER - Texas Tech University Health Science Center; CHUNG, EUNHEE - Texas Tech University Health Science Center; Cao, Jay

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/6/2022
Publication Date: 1/4/2023
Citation: Shen, C., Dufour, J.M., Miranda, J.M., Kaur, G., Chung, E., Cao, J.J. 2023. Effect of dietary geranylgeraniol and green tea polyphenols on glucose homeostasis, bone turnover biomarkers, and bone microstructure in obese mice. Nutrients. 24(2):1-12. https://doi.org/10.3390/ijms24020979.
DOI: https://doi.org/10.3390/ijms24020979

Interpretive Summary: Obesity, type 2 diabetes (T2DM), and osteoporosis are major global health concerns over the last few decades. Data indicate that obesity and T2DM are detrimental to bone health. Dietary supplements, bioactive components, nutraceuticals, and botanicals (collectively called functional foods) have been used to prevent or alleviate the complications of obesity/T2DM on bone health. In this study, we investigated combined effects of geranylgeraniol (GGOH, a bioactive compound found in fruits and vegetables) and green tea polyphenols (GTP) on glucose homeostasis and bone remodeling in obese mice. We found that either GGOH or GTP supplementation improved glucose tolerance, insulin sensitivity, and bone structural parameters in obese mice. The combination of GGOH and GTP may have additive effects on bone by suppressing inflammation. Our results demonstrate that supplementation of GGOH and GTP improves bone health in obese mice.

Technical Abstract: Previously, we demonstrated that the administration of either geranylgeraniol (GGOH) or green tea polyphenols (GTP) improved bone health. This study examined the combined effects of GGOH and GTP on glucose homeostasis and bone remodeling in obese mice. We hypothesized that GGOH and GTP would have an additive or synergistic effect on improving glucose homeostasis and bone remodeling via suppression of proinflammatory cytokines. Forty-eight male C57BL/6J mice were assigned to a high-fat diet (control), HFD+400mg GGOH/kg diet (GG), HFD+0.5%GTP water (TP), or HFD+GGOH+GTP (GGTP) diet for 14 weeks. Results demonstrated that individual GGOH and GTP supplementation improved glucose tolerance and insulin sensitivity in obese mice. Neither GGOH nor GTP affected (1) pancreas insulin or bone formation procollagen type I intact N-terminal, (2) bone volume at the lumbar vertebrae, or (3) bone parameters at the trabecular bone and cortical bone of the femur. There was an interactive effect for serum bone resorption collagen type 1 cross-linked C-telopeptide levels, resulting in no-GGOH and no-GTP groups having the highest values. GGOH increased trabecular number and decreased trabecular separation at the lumbar vertebrae. GTP increased trabecular thickness at lumbar vertebrae. The GG group produced the greatest connectivity density (Conn.Dn) and the lowest structure model index. Only GTP, not GGOH, decreased adipokines levels (resistin, leptin, monocyte chemoattractant protein-1, and interleukin-6). This study suggests that GGOH and GTP each improve bone microarchitecture and glucose homeostasis, and that the combination of GGOH and GTP may have additive effects on trabecular structure likely via a suppression of inflammation.