(P30-006-25) Suppression of Renal Pro-inflammatory Cytokines by Fructooligosaccharides Is Associated With Renal Vitamin D Signaling in High-Fat Diet-Induced Obese C57BL/6 Mice

Objectives: Studies have shown that 24%-33% of kidney disease cases are associated with obesity. Kidneys are important sites for activating vitamin D (VD) and subsequent immune system regulation. Compromised renal function could lead to VD deficiency and autoimmune complications. Though prebiotic fiber has previously been shown to improve kidney health and restore VD status in type 2 diabetic rats, the effect of FOS on obesity-associated kidney complications is unknown. Here, we aim to investigate the effect of FOS on kidney function and inflammation in an obese state.

Methods: Male and female C57BL/6J mice at 5-week-old were randomized into 4 groups (n = 10/group) to receive 1) standard AIN-93G control diet (CON), 2) CON + 5% FOS (CON-FOS), 3) High fat diet (60% kcal from fat; HFD), or 4) HFD + 5% FOS (HFD-FOS) for 10 weeks. Urine and kidney were collected for determination of kidney function, renal VD receptor (VDR) and cytokines expressions.

Results: Compromised kidney function, as indicated by higher urinary protein and low urinary creatinine, was observed in HFD-fed mice compared to CON mice, unaffected by FOS interventions. Renal VD signaling, measured by the mRNA expression of Vdr, was attenuated in HFD mice compared to CON mice. FOS further downregulated renal Vdr expressions in HFD mice by approximately 50% compared to mice on HFD alone (P < 0.01). The mRNA expression of renal pro-inflammatory cytokines, Il-1β, Il-6, and Tnfα measured renal inflammation. Female mice exhibited greater renal Il-6 and Tnfα expressions compared to male mice. While FOS did not affect CON-fed mice (CON-FOS), it attenuated the expressions of Il-1β and Tnfα by 2-fold (P < 0.01) and 1.4-fold (P < 0.01), respectively, in HFD mice (HFD-FOS) compared to mice on HFD alone. Furthermore, a positive correlation was observed between renal Vdr and Il-1β (r = 0.73; P < 0.01), Il-6(r = 0.69; P < 0.01), and Tnfα (r = 0.88; P < 0.01), respectively.

Conclusions: Our results demonstrated that FOS may suppress kidney inflammation in high-fat diet-fed mice, a mechanism likely regulated by VD activation. FOS may serve as a novel strategy to optimize VD status for the prevention of obesity-associated kidney complications.

Funding Sources: This study was supported by the Undergraduate Research Fellowship granted to Ms. Emily Butler and the Research Enhancement Fund granted to Dr. Gar Yee Koh by Texas State University.