Hepatic Mitochondrial Alterations in GLP-1 Poor Responders Undergoing Roux-en-Y Gastric Bypass

GLP-1 receptor agonist–refractory obesity patients undergoing Roux-en-Y gastric bypass show greater baseline hepatic lipid accumulation and mitochondrial ultrastructural abnormalities, with reduced AMPK-ACC phosphorylation.

• Why it matters: It is unclear whether inadequate GLP-1 RA weight-loss response is linked to distinct hepatic metabolic abnormalities and altered postoperative recovery after metabolic surgery.
• What they did: In a prospective observational study, 20 RYGB patients (10 GRO with <5% total body weight loss after ≥6 months GLP-1 RA therapy, 10 GLP-1 RA–naive GNO) and 5 lean controls had paired liver biopsies at surgery and ~6 months, assessed by histology, BODIPY fluorescence, transmission electron microscopy, and Western blots.
• The result: Both cohorts lost substantial weight by six months (25.21% vs 29.51% total weight loss), but GRO had smaller postoperative improvements and persisted lower postoperative AMPK/ACC phosphorylation ratios plus reduced SDHB, UQCRC2, COX IV, and ATP5A despite comparable NDUFS8.