Soluble dietary fiber from Piper sarmentosum Roxb. leaves modulates gut microbiota-derived cis-11-eicosenoic acid to regulate lipid metabolism.

Obesity represents a critical global health challenge, significantly elevating risks for major chronic diseases. This underscores the urgent necessity to develop innovative prevention and therapeutic interventions. While Piper sarmentosum Roxb. has demonstrated antidiabetic and antihypertensive properties, its anti-obesity effects and underlying mechanisms remain largely uncharacterized. This study aimed to evaluate the anti-obesity effects of soluble dietary fiber from Piper sarmentosum Roxb. leaves (PSDF) and elucidate its molecular basis. PSDF was characterized as an acidic dietary fiber, predominantly composed of galacturonic acid (55.64%), galactose (21.74%), and arabinose (11.97%), exhibiting a triple-helical conformation and high thermal stability. In diet-induced obese mice, six weeks of PSDF administration significantly ameliorated glucose and lipid metabolic disorders (p < 0.05), an effect associated with modulation of gut microbiota. Untargeted metabolomics identified cis-11-eicosenoic acid (GA) as a key metabolite. In a 3T3-L1 single-cell model, GA treatment did not affect adipocyte differentiation. However, in a co-culture model of 3T3-L1 adipocytes and RAW264.7 macrophages, GA significantly downregulated pro-inflammatory cytokines (IL-1β, TNF-α) and SREBF1 expression, while upregulating anti-inflammatory markers (IL-4, IL-10) and fatty acid oxidation genes (CPT1A, PGC-1α). These results initially suggested that GA may exert anti-obesity effects primarily through modulating inflammation-associated lipid metabolism pathways. Fecal microbiota transplantation (FMT) confirmed both GA elevation and anti-adiposity effects were microbiota-dependent. These findings demonstrated PSDF alleviated lipid accumulation by modulating a gut microbiota-adipose axis centered on GA production, thereby improving inflammation-mediated lipid metabolism. This newly elucidated microbiota-GA axis establishes a theoretical basis for developing PSDF-based soluble dietary fibers into microbiota-focused anti-obesity nutraceuticals.