Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation.

BACKGROUND

Obesity serves as a predominant factor in the progression of metabolic syndrome and type 2 diabetes mellitus. While sleeve gastrectomy (SG) is a well-established surgical intervention, its impact on appetite-regulating hormones, such as ghrelin (GHRL), is limited. Sleeve gastrectomy combined with fundoplication (SGFD) has emerged as a potential strategy to improve metabolic outcomes by modifying both gastric anatomy and gut-brain signaling.

METHODS

Sixty-five Sprague-Dawley rats were enrolled. After 8 weeks of high-fat feeding, 48 rats developed diet-induced obesity (DIO). These rats were randomized into four experimental groups: DIO control, sham-operated, SG, and SGFD, alongside a normal control cohort. Biochemical indicators, hormonal fluctuations, and insulin responsiveness were analyzed. Molecular expressions were evaluated through quantitative real-time polymerase chain reaction and Western blotting.

RESULTS

SGFD reduced body weight (-24.7%), food intake (-28.3%), fasting glucose (-37.5%), triglycerides (-42.6%), and serum GHRL (-51.2%) compared with the DIO group (P<0.01). Gastric GHRL, preproghrelin, and ghrelin O-acyltransferase (GOAT) expression were suppressed. Hypothalamic neuropeptide Y (NPY) was downregulated, and AMP-activated protein kinase (AMPK) signaling was robustly enhanced across various tissues. SGFD also improved insulin receptor substrate-1 (IRS-1), glucose transporter type 4 (GLUT4), β-cell function, hepatic lipid oxidation, and brown adipose thermogenesis. SGFD outperformed SG in most metabolic and molecular outcomes (P<0.05).

CONCLUSION

SGFD provides superior metabolic benefits over SG alone by suppressing GHRL signaling and activating systemic AMPK pathways. SGFD represents a promising surgical strategy for obesity and metabolic syndrome.