450-nm Blue Laser-Induced Gastric Mucosal Ablation Promotes Short-Term Weight Loss and Metabolic Benefits in Rats with Obesity.

OBJECTIVES: This study aimed to evaluate the effects and potential mechanisms of gastric mucosal ablation (GMA) using a 450-nm blue laser on weight loss and metabolic outcomes. METHODS: Male Sprague-Dawley rats were fed a 45% high-fat diet (HFD) for 15 weeks to induce obesity. Rats with obesity were then randomly assigned to the GMA group (n = 26) or the sham surgery group (n = 24). The GMA group received 450-nm blue laser-induced ablation (power: 5 W), targeting approximately 70% of the gastric mucosa. Body weight and food intake were recorded weekly. At 2, 4, and 8 weeks postoperatively, eight rats per group were randomly selected for oral glucose tolerance testing and fasting serum collection for biochemical analyses, including lipid profile, blood glucose, insulin, and ghrelin. Liver and gastric tissues were collected for histological analysis, including Oil Red O staining and immunofluorescence. Moreover, hepatic transcriptomics, western blot analyses, and hepatic lipid profiling were performed. RESULTS: Over the 8-week postoperative period, GMA significantly reduced body weight and food intake and improved glucose and lipid metabolism in rats with obesity compared with the sham surgery group. Gastric mucosal remodeling occurred following GMA, characterized by a reduction in ghrelin-positive cells and serum ghrelin levels, along with an increase in glucagon-like peptide-1-positive cells. Hepatic transcriptomics, western blot, and hepatic lipid profiling analyses revealed that GMA was associated with a reversal of HFD-induced suppression of the peroxisome proliferator-activated receptor-α (PPARα) pathway, accompanied by enhanced fatty acid metabolism signatures and reduced hepatic lipid accumulation. CONCLUSIONS: 450-nm blue laser-induced GMA demonstrated short-term effects in weight loss and metabolic improvement, accompanied by changes in ghrelin levels and hepatic PPARα pathway. Further studies are warranted to elucidate the long-term effects and more intricate mechanisms.