Sleeve Gastrectomy Reverses Hepatic and Circulating Transcriptomic Dysregulation by Restoring Lipid and Energy Metabolism in a Diet-Induced MASLD 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.

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 (PCR) 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) please give in full and then abbreviations in parentheses when a term appears for the first time. Pathway analysis demonstrated significant modulation of peroxisome proliferator-activated receptor (PPAR) and adenosine monophosphate-activated protein kinase (AMPK) 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 non-invasive monitoring and therapeutic intervention.