(P30-019-25) Fructooligosaccharide Upregulates Colonic Vitamin D Receptors and Modulates Inflammatory Status in High-Fat Diet-Induced Obese Male C57BL/6 Mice

Objectives: The prevalence of vitamin D (VD) deficiency is 35% greater in individuals with obesity compared to non-obese, increasing their risk for metabolic complications. Previously, we demonstrated that fructooligosaccharide (FOS), when consumed along with VD supplementation, upregulated colonic vitamin D receptor (VDR) and attenuated anxiety-related behavior in lean mice compared to mice fed VD alone. Due to the immunomodulatory role of VD, it is hypothesized that FOS can serve as an effective dietary intervention for prevention of chronic inflammation commonly observed in obesity. The current study aims to explore the effect of FOS on VD signaling and their impacts on metabolic changes and inflammatory status in high-fat diet-induced (HFD) obese mice.

Methods: Male C57BL/6J mice at 5-week-old were randomized (n = 10/group) to receive 1) standard AIN-93G control diet (CON), 2) CON + 5% FOS (CON-FOS), 3) HFD (60% kcal from fat), or 4) HFD + 5% FOS (HFD-FOS) for 10 weeks. Serum and colonic mucosa were collected for analyses of VD signaling and pro-inflammatory cytokines.

Results: Body weight of HFD mice was 1.6-fold greater than in CON mice after 10-week of intervention (P < 0.001), yet FOS did not alter body weight in mice fed either diet. HFD mice exhibited lower VD status (P = 0.037), as measured by serum 25-hydroxycholecalciferol (25D), and 70% lower in colonic Vdr mRNA expression (P = 0.038) compared to CON mice. Though FOS did not affect serum 25D levels in either CON or HFD mice, mRNA expression of colonic Vdr was upregulated by 2-fold in mice of HFD-FOS compared to HFD (P < 0.01). A lowering trend was observed with mRNA expression of colonic Toll-like receptor 4 (Tlr4) in HFD-FOS mice compared to HFD mice (P = 0.068), which was negatively correlated to colonic Vdr expression (r = -0.747; P < 0.01). Additionally, FOS suppressed the elevation of circulating IL-6 by 44% in HFD mice (P = 0.038), and that it did not differ from CON mice.

Conclusions: We showed that FOS suppressed VDR activation in the colon and attenuated colonic inflammation in HFD-induced obese mice possibly via the inhibition of TLR4 signaling pathway. Taken together, FOS may serve as a potential dietary intervention for the prevention of gastrointestinal complications associated with obesity phenotype.

Funding Sources: This study was supported by Texas State University Research Enhancement Fund granted to Dr. Gar Yee Koh.