Diabetes, Metabolic Syndrome and Obesity · 5 authors, 2 centres
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In obese T2DM rats induced by high-fat diet and streptozotocin, Roux-en-Y gastric bypass improved insulin sensitivity and reduced triglyceride levels by upregulating the Grin3a/AMPK signal axis in the hypothalamic arcuate nucleus, an effect reversed by Grin3a knockdown.
This preclinical study used an obese T2DM rat model constructed by high-fat diet feeding and streptozotocin injection, treated with Roux-en-Y gastric bypass (RYGB). Grin3a shRNA was injected into bilateral hypothalamic arcuate nucleus (ARC) to knock down Grin3a expression. Eight weeks post-operation, metabolic parameters (body weight, FBG, FSI, HOMA-IR, plasma TG) were assessed alongside Western blot and qRT-PCR for Grin3a, AMPK, and p-AMPK expression in ARC. RYGB reduced FBG, FSI, HOMA-IR, and plasma TG levels while increasing Grin3a expression and p-AMPK/AMPK ratio in ARC. Grin3a knockdown reversed these RYGB-induced metabolic improvements and reduced p-AMPK/AMPK ratio. Study limitations include that the mechanism of Grin3a regulation of AMPK and downstream AMPK targets were not deeply explored, and findings require further verification such as via Grin3a over-expression or AMPK inhibition experiments.
