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Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3508-3526页

作者： Shuyi Wang Jun Tao Huaguo Chen machender r.kandadi Mingming Sun Haixia Xu Gary D.Lopaschuk Yan Lu Junmeng Zheng Hu Peng Jun ren Department of Emergency Shanghai Tenth People's HospitalSchool of Medicine Tongji UniversityShanghai 200072China Shanghai University School of Medicine Shanghai 200044China University of Wyoming College of Health Sciences LaramieWY 82071USA Department of Cardiovascular Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510000China Medprime Health Services LLC ParisTX 75460USA Department of Cardiology Shanghai Institute of Cardiovascular DiseasesZhongshan Hospital Fudan UniversityShanghai 200032China Department of Cardiology Affiliated Hospital of Nantong UniversityNantong 226001China Cardiovascular research Centre University of AlbertaEdmontonAlberta T6G 2S2Canada Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationDepartment of Endocrinology and MetabolismZhongshan Hospital Fudan UniversityShanghai 200032China Department of Laboratory Medicine and Pathology University of WashingtonSeattleWA 98195USA

Given the opposing effects of Akt and AMP-activated protein kinase(AMPK)on metabolic homeostasis,this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic ***2–Ampkα2 double knockout(DKO)mice were placed on high fat diet for 5 *** metabolism,energy homeostasis,cardiac function,lipid accumulation,and hepatic steatosis were *** mice were lean without anthropometric *** fat intake led to adiposity and decreased respiratory exchange ratio(rEr)in wild-type(WT)mice,which were ablated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** fat intake increased blood and hepatic triglycerides and cholesterol,promoted hepatic steatosis and injury in WT *** effects were eliminated in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** diet promoted fat accumulation,and enlarged adipocyte size,the effect was negated in DKO *** intake elevated fatty acid synthase(FAS),carbohydrate-responsive element-binding protein(CHrEBP),sterol regulatory element-binding protein 1(SrEBP1),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),peroxisome proliferator-activated receptor-α(PPArα),PPArγ,stearoyl-CoA desaturase 1(SCD-1),phosphoenolpyruvate carboxykinase(PEPCK),glucose 6-phosphatase(G6Pase),and diglyceride O-acyltransferase 1(DGAT1),the effect was absent in DKO but not Akt2^(-/-) and Ampkα2^(-/-) *** diet dampened mitophagy,promoted inflammation and phosphorylation of forkhead box protein O1(FoxO1)and AMPKα1(Ser^(485)),the effects were eradicated by *** of Parkin effectively nullified DKO-induced metabolic benefits against high fat *** samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B(LC3B),Pink1,Parkin,as well as enhanced phosphorylation of Akt,AMPK(Ser^(485)),and FoxO1,which were consolidated by rNA sequencing(rNAseq)and mass spectrometry analyses from rodent and human *** data suggest that concurrent de

关键词： Akt2 AMPK Parkin High fat intake Obesity Steatosis Mitophagy FoxO1

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Author correction to‘Ablation of Akt2 and AMPKα2 rescues high fat diet-induced obesity and hepatic steatosis through Parkin-mediated mitophagy’[Acta Pharmaceutica Sinica B 11(2021)3508-3526]

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Acta Pharmaceutica Sinica B 2023年第2期13卷 897-898页

The authors of the above-mentioned paper noticed an error in Fig.5a as reported.H&E staining was shown in wrong color during figure processing and DKO-LF group was accidently copied and pasted *** H&E images have been replaced with the correct color with the accurate grouping *** text content in figure legend or conclusion is affected by this *** authors sincerely apologize for any inconvenience caused to the journal and readers.

关键词： correction journal mentioned

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Tween 80 containing lipid nanoemulsions for delivery of indinavir to brain

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Acta Pharmaceutica Sinica B 2013年第5期3卷 345-353页

作者： kandadi Prabhakar Syed Muzammil Afzal Goparaboina Surender Veerabrahma Kishan Nanotechnology Laboratory Department of PharmaceuticsUniversity College of Pharmaceutical SciencesKakatiya UniversityWarangal 506009India

Indinavir is a protease inhibitor used in the treatment of HIV ***,it has limited efficacy in eradicating the virus in the brain due to efflux by P-glycoprotein(P-gp)expressed at the blood–brain barrier(BBB).The objective of this work was to develop an o/w lipid nanoemulsion(LNE)of indinavir using Tween 80 as co-emulsifier to improve its brain specific *** were prepared with different compositions and were characterized for globule size,polydispersity index,zeta potential and in vitro drug *** formulations were then evaluated for drug content,entrapment efficiency and stability after which brain uptake studies were carried out using fluorescent labeled LNEs and pharmacokinetic(PK)and tissue distribution studies were conducted after intravenous administration in *** uptake of indinavir was shown to be improved for a 1%Tween 80 containing formulation(F5)compared to a formulation containing 0.3%cholesterol(F2).In PK studies,the brain level of indinavir subsequent to administration of F5 was significantly(Po0.05)higher than produced by administration of a drug solution(2.44-fold)or a control nanoemulsion(F1)(1.48-fold)or formulation F2(1.6-fold).The increased brain specific accumulation of indinavir from F5 is probably due to enhanced low density lipoprotein-mediated endocytosis and P-gp inhibition by Tween 80 at the *** results suggest Tween 80 containing LNEs could provide a simple but effective means of delivering indinavir to brain.

关键词： Tween 80 Indinavir Lipid nanoemulsions Brain delivery Therapeutic availability Fluorescent DiD oil

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