ArticleCirculation research2018
(Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis.
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Article in Circulation research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
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35 citing papers in PubMed, 61 citations in OpenAlex.
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- A charge reversal nano-assembly prevents hepatic steatosis by resolving inflammation and improving lipid metabolism.Bioactive materials · 2025Article
- Crosstalk between renin and arachidonic acid (and its metabolites).Lipids in health and disease · 2025Review
- Pro-renin Receptor (PRR) as a Target to Reduce Non-alcoholic Fatty Liver Disease Post Liver Transplantation.Current medicinal chemistry · 2025Review
- Soluble (pro)renin receptor as a novel laboratory biomarker of atherosclerosis.Acta biochimica et biophysica Sinica · 2024Article
- Nephron specific ATP6AP2 knockout increases urinary excretion of fatty acids and decreases renal cortical megalin expression.Scientific reports · 2024Article
- Assessment of the (Pro)renin Receptor Protein Expression in Organs.Current issues in molecular biology · 2024Article
- (Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway.Journal of translational medicine · 2024Article
- (Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet-Induced Hepatic Steatosis.Biomolecules · 2023Article
- The role of (pro)renin receptor and its soluble form in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Soluble (Pro)Renin Receptor Level in Patients with Severe Obesity Is Associated with Visceral Adiposity and Is Involved with Insulin Resistance and Renal Injury.Obesity facts · 2023Article
- Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis.Clinical and molecular hepatology · 2023Review
- Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis.JCI insight · 2022Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- Renin-Angiotensin System in Liver Metabolism: Gender Differences and Role of Incretins.Metabolites · 2022Review
- The LOX-1 receptor ectopically expressed in the liver alleviates atherosclerosis by clearing Ox-LDL from the circulation.Molecular medicine (Cambridge, Mass.) · 2022Article
- Antisense oligonucleotide is a promising intervention for liver diseases.Frontiers in pharmacology · 2022Review
- Function of the endolysosomal network in cholesterol homeostasis and metabolic-associated fatty liver disease (MAFLD).Molecular metabolism · 2021Review
- Taurine-Mediated IDOL Contributes to Resolution of Streptococcus uberis Infection.Infection and immunity · 2021Article
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19 authors at 5 institutions in 3 countries.
Liwei RenFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Yuan SunFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Hong LuFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Dien YeFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Lijuan HanFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Na WangFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Alan DaughertyFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Furong LiFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Miaomiao WangFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Fengting SuFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Wenjun TaoFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Jie SunFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Noam ZelcerFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Adam E MullickFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
A H Jan DanserFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Yizhou JiangFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Yongcheng HeFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.).
Xiongzhong RuanFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.). x.lu@szu.edu.cn xiongzruan@gmail.com.
Xifeng LuFrom the AstraZeneca-Shenzhen University Joint Institute of Nephrology, Department of Physiology, Shenzhen University Health Science Center, Shenzhen University, China (L.R., Y.S., D.Y., L.H., N.W., M.W., F.S., W.T., J.S., X.R., X.L.); Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China (L.R., Y.S., F.L., X.L.); Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam University, The Netherlands (L.R., Y.S., A.H.J.D.); Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky, Lexington (H.L., A.D.); Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (N.Z.); Ionis Pharmaceuticals, Inc, Carlsbad, CA (A.E.M.); Institute for Advanced Study, Shenzhen University, China (Y.J.); The First Affiliated Hospital of Shenzhen University, China (Y.H.); and John Moorhead Laboratory, Center for Nephrology, University College London, United Kingdom (X.R.). x.lu@szu.edu.cn xiongzruan@gmail.com.
Academic Medical Center · NLErasmus MC · NLIonis Pharmaceuticals (United States) · USJinan University · CNShenzhen University · CN
Funding
Cell and molecular studies in cardiovascular engineeringR01HL064388 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2001 to 2005
$6.9MEpigenetic regulation of endothelial phenotype by flow and hypercholesterolemia in vivo and in vitroK99HL127272 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI JIANG, YIZHOU · 2016 to 2017
$216kEuropean Research Council 617376NHLBI NIH HHS K99 HL127272NHLBI NIH HHS R01 HL064388
Abstract
rationaleAn elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin-angiotensin system.
objectivesTo investigate the physiological role of (P)RR in lipid metabolism in vivo. METHODS AND
resultsWe used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis.
conclusionsCollectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism.
Indexed as
Lipid MetabolismAcetyl-CoA CarboxylaseAdaptor Proteins, Vesicular TransportAnimalsCells, CulturedDiet, High-FatFatty LiverGene SilencingHepatocytesHep G2 CellsHumansMaleMiceMice, Inbred C57BLObesityProrenin ReceptorAcetyl-CoA CarboxylaseAdaptor Proteins, Vesicular TransportProrenin ReceptorPyruvate Dehydrogenase ComplexReceptors, Cell SurfaceSortilindyslipidemiahypercholesterolemiahypertriglyceridemialiverrenin–angiotensin systemvacuolar H+-ATPase
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