Investigation of peroxisome proliferator activated receptors in inulin supplemented mice

Inulin is a prebiotic that is selectively fermented in the gut to short-chain fatty acids—especially butyrate—and can influence the epithelial barrier and host metabolism via nuclear receptor pathways governed by PPAR isoforms (PPAR-α/β/γ). Yet, how inulin shapes tissue-specific PPAR responses along the gut–liver axis, and how these responses relate to microbiota-derived metabolites, remains insufficiently defined. This thesis aimed to delineate the colonic and hepatic PPAR responses to inulin in mice and to map accompanying morphological and metabolic changes in an integrated manner. Adult male C57BL/6 mice were assigned to Control and Inulin groups; the inulin group received 10% inulin in drinking water for 7 weeks under ad libitum feeding. At study end, body weight and systemic metabolic readouts (blood glucose and β-hydroxybutyrate) were recorded; intestinal segment lengths and, in particular, cecal weight were assessed. RNA was isolated from liver and colon epithelium to quantify PPAR-α/β/γ mRNA levels by RT-PCR. As a functional output of microbial activity, fecal butyrate concentrations were measured. Appropriate statistical tests were used to compare groups. Inulin increased cecal weight and elevated fecal butyrate levels, consistent with enhanced fermentative activity. Systemically, there were no notable differences in body weight, blood glucose, or ketone measures between groups. At the molecular level, hepatic expression of PPAR isoforms remained largely unchanged, whereas colonic PPAR-γ expression increased. Taken together, these findings indicate that inulin triggers a colon-specific PPAR-γ response associated with shifts in microbiota-derived metabolites, while remaining dissociable from systemic metabolic indicators. In conclusion, inulin enhances microbiota-derived butyrate and strengthens colonic PPAR-γ signaling, offering a mechanistic, diet-based intervention that supports epithelial homeostasis. By resolving tissue specificity along the gut–liver axis, this work provides a foundation for future studies on dose/duration optimization, protein-level validation, and functional epithelial outcomes (e.g., barrier integrity, mucus dynamics).