Does LKB1 Mediate Activation of Hepatic AMP-Protein Kinase (AMPK) and Sirtuin1 (SIRT1) After Roux-en-Y Gastric Bypass in Obese Rats?
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Roux-en-Y gastric bypass (RYGB) improves steatosis and reduces liver triglycerides in obese rats. Sirtuin1 (SIRT1) and AMP-activated protein kinase (AMPK) are key metabolic regulators that reduce lipogenesis and increase fatty acid oxidation. LKB1 phosphorylates AMPK and may activate SIRT1. We hypothesize that RYGB in obese rats is associated with an upregulation of the LKB1–AMPK–SIRT1 signaling pathway.
Obese Sprague–Dawley male rats underwent RYGB or sham. Liver tissue was obtained at 9 weeks postoperatively. Protein levels of SIRT1, LKB1, p-LKB1, AMPKα, p-AMPKα, and p-protein kinase C-ζ (PKC-ζ) were determined. Protein associations of LKB1 with each of SIRT1, AMPKα, and PKC-ζ were determined by co-immunoprecipitation. Data are mean ± SD; for t test, p < 0.05 was significant.
RYGB increased protein levels of hepatic AMPKα, p-AMPKα, and SIRT1 (all p < 0.001 vs. sham); p-LKB1 but not LKB1 increased after RYGB (p < 0.001 vs. sham). Physical interactions of LKB1–AMPK and LKB1–SIRT1 increased after RYGB (p < 0.001 vs. sham). Although PKC-ζ mRNA and p-PKC-ζ did not change, interactions between LKB1 and PKC-ζ increased after RYGB (p < 0.001 vs. sham).
RYGB increases hepatic levels of SIRT1, AMPK, and p-AMPK as well as increasing interactions of LKB1 with AMPK or SIRT1. p-PKC-ζ may play an intermediary role in the interaction between AMPK and SIRT. These findings demonstrate key signaling changes in powerful metabolic regulators that may account for the resolution of steatosis after RYGB.
KeywordsLKB1 AMPK SIRT1 Roux-en-Y gastric bypass Obesity
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