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Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice.

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机构： [1]Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA [2]State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen, China [3]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, China [4]Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, China

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关键词： AMPKA1/PRKAA1 endothelial cells inflammation metabolism

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Excess nutrient-induced endothelial cell inflammation is a hallmark of high fat diet (HFD)-induced metabolic syndrome. Pharmacological activation of the protein kinase AMP-activated α1 (PRKAA1) also known as AMPKα1, shows its beneficial effects in many studies of cardiometabolic disorders. However, AMPKα1, as a major cellular sensor of energy and nutrients in endothelial cells, has not been studied for its physiological role in excess nutrient-induced endothelial cell (EC) inflammation.Wild-type and EC-specific Prkaa1 knockout mice were fed with an HFD. Body weight, fat mass composition, glucose, and lipid levels were monitored regularly. Insulin sensitivity was analysed systemically and in major metabolic organs/tissues. Inflammation status in metabolic organs/tissues were examined with quantitative RT-PCR and flow cytometry. Additionally, metabolic status, inflammation severity, and signalling in cultured ECs were assayed with multiple approaches at the molecular level.EC Prkaa1 deficiency unexpectedly alleviated HFD-induced metabolic syndromes including decreased body weight and fat mass, enhanced glucose clearance and insulin sensitivity, and relieved adipose inflammation and hepatic steatosis. Mechanistically, PRKAA1 knockdown in cultured ECs reduced endothelial glycolysis and fatty acid oxidation, decreased levels of acetyl-CoA and suppressed transcription of inflammatory molecules mediated by ATP citrate lyase and histone acetyltransferase p300.This unexpected pro-inflammatory effect of endothelial AMPKα1/PRKAA1 in a metabolic context provides additional insight in AMPKα1/PRKAA1 activities. An in-depth study and thoughtful consideration should be applied when AMPKα1/PRKAA1 is used as a therapeutic target in the treatment of metabolic syndrome.© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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出版当年[2020]版中科院分区表Review为是的期刊

：

大类 | 2 区

医学

小类 | 1 区药学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区药学

第一作者：

第一作者机构： [1]Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA

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通讯机构： [1]Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA [*1]Vascular Biology Center, Department of Cellular Biology and Anatomy Medical College of Georgia, Augusta University, Augusta, GA 30912, USA

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