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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: METHODS, RESULTS. Meshes: AMP-Activated Protein Kinases, Animals, Body Weight, Diet, High-Fat, Down-Regulation, Endothelial Cells, Endothelium, Vascular, Male, Mitochondria, Nitric Oxide Synthase Type III, Phosphatidylinositol 3-Kinases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Rats, Sprague-Dawley, Signal Transduction, Superoxide Dismutase.
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Does high-fat diet induce endothelial dysfunction through a down-regulation of the endothelial AMPK-PI3K-Akt-eNOS pathway? Context: Activation of endothelial adenosine monophosphate-activated protein kinase (AMPK) contributes to increase nitric oxide (NO) availability. The aim of this study was to assess if high-fat diet (HFD)-induced endothelial dysfunction is linked to AMPK deregulation. Twelve-week-old Sprague Dawley male rats were assigned either to control (10 kcal % from fat) or to HFD (45 kcal % from fat) for 8 wk. HFD rats segregated in obesity-prone (OP) or obesity-resistant (OR) rats according to body weight. HFD triggered an impaired glucose management together with impaired endothelium-dependent relaxation, reduced endothelial AMPK activity and lower NO availability in aortic rings of OP and OR cohorts. Relaxation evoked by AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) was reduced in both OP and OR rings, which exhibited lower p-AMPKα-Thr(172) /AMPKα ratios that negatively correlated with plasma non-esterified fatty acids (NEFA) and triglycerides (TG). Inhibition of PI3K (wortmannin, 10(-7) M) or Akt (triciribine, 10(-5) M) reduced relaxation to AICAR only in the control group (p < 0.001). Akt (p-Akt-Ser(473) ) and eNOS phosphorylation (p-eNOS-Ser(1177) ) were significantly reduced in OP and OR (p < 0.01).
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Endothelial dysfunction caused by HFD is related to a dysfunctional endothelial AMPK-PI3K-Akt-eNOS pathway correlating with the increase of plasma NEFA, TG, and an impaired glucose management. Final Decision: yes