Solenocera crassicornis Peptides (SCPs) improve metabolic, hepatic, and intestinal markers in HFD-obese mice during diet normalization

The global obesity epidemic drives a cascade of metabolic dysfunction, often characterized by systemic oxidative stress, compromised gut barrier integrity, and disruption of the crucial gut-liver axis. Current therapeutic strategies frequently fall short in comprehensively addressing these interconnected pathologies, highlighting a critical need for novel interventions. Marine-derived bioactive compounds, such as peptides, are gaining attention for their potential to modulate these pathways, offering a promising avenue for improving metabolic health by targeting the gut and liver.

Obese male C57BL/6J mice, induced by 7 weeks of high-fat diet (HFD) feeding, were subsequently switched to a normal diet and orally administered either vehicle, orlistat, or Solenocera crassicornis peptides (SCPs) for 4 weeks. The SCPs were extensively characterized using UPLC-Q-TOF-MS/MS and amino acid analysis, with bioactivity predictions and Keap1 docking performed. Researchers assessed adipose tissue mass, serum lipid profiles, liver histology, hepatic antioxidant status, and intestinal barrier markers including diamine oxidase levels. Gut microbiota composition was analyzed via 16S rRNA sequencing. Additionally, a simulated digestion-fecal fermentation model evaluated SCP fermentation products on H2O2-induced oxidative injury and MUC2 secretion in LS174T goblet-like cells.

Administration of SCPs during diet normalization led to significant improvements across multiple metabolic and physiological parameters. The peptides notably reduced epididymal and perirenal fat mass, alongside improved serum lipid profiles. Hepatic analysis revealed improved steatosis-related morphology and an enhanced hepatic antioxidant status. Intestinal health also benefited, with improved intestinal morphology and increased mucin-associated staining, indicating enhanced barrier function. Furthermore, SCPs were associated with decreased serum diamine oxidase levels and reduced hepatic lipopolysaccharide accumulation, suggesting a stronger gut barrier and reduced endotoxemia. 16S rRNA sequencing demonstrated SCP-associated microbial shifts, with specific correlations linking altered taxa to improved metabolic and barrier markers.

Fermentation products generated in the presence of digested SCPs significantly improved readouts related to oxidative stress and MUC2 secretion in LS174T cells, confirming direct cellular benefits.