Sleeve Gastrectomy Reverses Hepatic and Circulating Transcriptomic Dysregulation by Restoring Lipid and Energy Metabolism in Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease Rats

OBJECTIVES: This study aimed to identify key hepatic genes involved in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis and determine whether sleeve gastrectomy (SG) attenuates cafeteria diet-induced hepatic steatosis in a rat model. SUBJECT AND METHODS: Thirty-two male Sprague-Dawley rats were divided into four groups: control (lean), diet-induced obesity (DIO)-obese control, DIO-sham, and DIO-SG. Hepatic expression profiling of MASLD-associated genes was performed using RT2 Profiler polymerase chain reaction arrays. Circulating adipokines (leptin and adiponectin) and hepatic triglyceride (TG) content were also quantified. RESULTS: SG significantly reversed obesity-induced upregulation of key lipogenic (Fasn, Srebf1, Dgat2), gluconeogenic (G6pc, Gck), and inflammatory (Nfkb1, Il1b) genes, while enhancing fatty acid oxidation and mitochondrial pathways (Cpt2, Ppargc1a, Acadl). Pathway analysis demonstrated significant modulation of peroxisome proliferator-activated receptor and adenosine monophosphate-activated protein kinase signaling, fatty acid oxidation, and insulin sensitivity networks. Circulating leptin and hepatic TG content were significantly reduced following SG, consistent with systemic metabolic improvement. The normalization of Srebf1 and Dgat2 highlights restoration of hepatic lipid homeostasis and improved insulin sensitivity. CONCLUSION: SG reduced hepatic fat accumulation and mitigated MASLD through broad transcriptional and metabolic reprogramming of lipid, oxidative, and inflammatory pathways. The identification of shared hepatic-whole-blood signatures together with improvements in circulating biomarkers underscores the systemic impact of SG and suggests potential translational targets for noninvasive monitoring and therapeutic intervention.