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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #412862
Research Project: Modification of Diurnal Patterns to Promote Health in Models for Human Metabolic Dysfunction

Location: Dietary Prevention of Obesity-related Disease Research

Title: Inflammation suppressing effects of statin and annatto-extracted tocotrienol supplementation on bone microstructure, glucose homeostasis, and gut microbiota composition in obese mice

Author
item SHEN, CHWAN-LI - Texas Tech University Health Science Center
item WANKHADE, UMESH - University Of Arkansas
item SHANKAR, KARTIK - University Of Colorado
item NAJJAR, RAMI - Georgia State University
item FERESIN, RAFAELA - Georgia State University
item ELMASSRY, MOAMEN - Princeton University
item DUFOUR, JANNETTE - Texas Tech University Health Science Center
item KAUR, GURVINDER - Texas Tech University Health Science Center
item CHINTAPALLI, SREE - University Of Arkansas
item PICCOLO, BRIAN - University Of Arkansas
item DUNN, DALE - Texas Tech University Health Science Center
item Cao, Jay

Submitted to: Anticancer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/29/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Hyperglycemia, as seen in type 2 diabetes mellites, can increase free radical production and induce oxidative stress and inflammation. Increased oxidative stress and chronic inflammation can impair insulin signaling, bone metabolism, and muscle glucose transport. Dietary bioactive compounds can modify gut microbiota composition, reduce chronic inflammation and insulin resistance. This study investigated combined effects of tocotrienols, a dietary bioactive compound, and statin on glucose homeostasis, bone structure, and gut microbiome in obese mice. We demonstrated that tocotrienols combined with statin improved bone microstructure, glucose homeostasis, and microbial ecology like through reducing inflammation in obese mice.

Technical Abstract: This study examined the effects of tocotrienols (TT) in conjunction with statin on glucose homeostasis, bone microstructure, the gut microbiome, and systemic and liver inflammatory markers in obese C57BL/6J mice. Forty male C57BL/6J mice were fed a high=fat diet (HFD) and assigned to 4 groups (n=10/group) into a 2 (no statin vs 120 mg statin/kg diet) × 2 (no TT vs 400 mg TT/kg diet) factorial design for 14 weeks. Statin and TT improved glucose tolerance only when each was given alone, while only statin supplementation decreased insulin resistance. Consistently, only statin supplementation decreased serum insulin levels and HOMA-IR. Pancreatic insulin was also increased with statin treatment alone. Statin and TT alone or combined reduced levels of serum IL-6 but only TT attenuated the increased in serum leptin levels induced by a HFD. Additionally, statin supplementation, but not TT, reduced hepatic inflammatory cytokine gene expression. Statin supplementation increased bone area/total area and connectivity density at LV-4, while TT supplementation increased bone area/total area, trabecular number and decreased trabecular separation at distal femur. Statin supplementation, but not TT, reduced hepatic inflammatory cytokine gene expression. Neither TT supplementation or statin supplementation statistically altered microbiome species evenness or richness. Yet, they altered the relative abundance of certain microbiome species. Most notably, both TT and statin supplementation increased the relative abundance of Lachnospiraceae UCG-006. Our data demonstrates that TT and statin collectively benefit bone microstructure, glucose homeostasis, and microbial ecology in obese mice. Such changes may be, in part, associated with suppression of inflammation in the host.