1544-P: Fructooligosacharides Supplementation Prevents Western Diet–Induced Hypothalamic Inflammation

Obesity is linked to 30-53% of new diabetes cases in the U.S. yearly. This project investigates how supplementation with fructo-oligosaccharides (FOS), a widely used dietary fiber, protects against diet induced obesity (DIO) by decreasing bodyweight (BW) and fat accumulation. The beneficial effects of FOS are largely attributed to the production of Short-Chain Fatty Acids (SCFA) through gut microbiota-mediated fermentation. Our findings indicate that supplementing a Western diet (WD) with 10% FOS for 8 weeks increases SCFA levels in the bloodstream, prevents weight gain in mice, and reduces markers of hypothalamic inflammation and microglial activation. Building on these findings, we further investigated the short-term effects of 7-day FOS supplementation. We found that adding 10% FOS to the WD completely prevented body weight gain and fat mass accumulation, while also lowering fasting blood glucose levels. Notably, mice treated with FOS maintained circadian oscillation of fuel utilization, as observed through the respiratory exchange ratio (RER), in contrast to WD-treated mice whose RER oscillation was disrupted within the first day of the diet. These protective effects were accompanied by reduced expression of hypothalamic interleukin-6 and iNOS after just 1 day of diet treatment. Taken together, our results suggest that early suppression of hypothalamic inflammation may be responsible for the beneficial effects of FOS supplementation. Understanding the mechanisms underlying the protective effects of FOS is a crucial step in developing new dietary strategies and therapeutic targets to address the obesity epidemic and its associated comorbidities.