PDE5 Inhibition Ameliorates Visceral Adiposity Targeting the miR-22/SIRT1 Pathway: Evidence From the CECSID Trial
Context:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.Objective:To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial ad...
Saved in:
| Published in | The journal of clinical endocrinology and metabolism Vol. 101; no. 4; pp. 1525 - 1534 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Oxford University Press
01.04.2016
Copyright by The Endocrine Society |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Context:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.Objective:To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs).Design:Randomized, double-blind, placebo-controlled study in type 2 diabetes.Patients and Intervention:A total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected.Main Outcomes and Measures:Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT.Results:Compared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafil's modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile.Conclusions:Treatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression. |
|---|---|
| AbstractList | Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.
To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs).
Randomized, double-blind, placebo-controlled study in type 2 diabetes.
A total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected.
Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT.
Compared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafil's modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile.
Treatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression. CONTEXT:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients. OBJECTIVE:To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs). DESIGN:Randomized, double-blind, placebo-controlled study in type 2 diabetes. PATIENTS AND INTERVENTION:A total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected. MAIN OUTCOMES AND MEASURES:Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT. RESULTS:Compared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafilʼs modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile. CONCLUSIONS:Treatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression. Context:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.Objective:To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs).Design:Randomized, double-blind, placebo-controlled study in type 2 diabetes.Patients and Intervention:A total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected.Main Outcomes and Measures:Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT.Results:Compared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafil's modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile.Conclusions:Treatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression. Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.CONTEXTVisceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2 diabetes patients.To investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs).OBJECTIVETo investigate whether PDE5i affect visceral adipose tissue (VAT), specifically epicardial fat (epicardial adipose tissue [EAT]), and what mechanism is involved, using microarray-based profiling of pharmacologically modulated microRNA (miRNAs).Randomized, double-blind, placebo-controlled study in type 2 diabetes.DESIGNRandomized, double-blind, placebo-controlled study in type 2 diabetes.A total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected.PATIENTS AND INTERVENTIONA total of 59 diabetic patients were randomized to receive 100-mg/d sildenafil or placebo for 12 weeks. Fat biopsies were collected in a subgroup of patients. In a parallel protocol, db/db mice were randomized to 12 weeks of sildenafil or vehicle, and VAT was collected.Anthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT.MAIN OUTCOME AND MEASURESAnthropometric and metabolic parameters, EAT quantification through cardiac magnetic resonance imaging, array of 2005 circulating miRNAs, quantitative PCR, and flow cytometry of VAT.Compared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafil's modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile.RESULTSCompared with placebo, sildenafil reduced waist circumference (P = .024) and EAT (P = .045). Microarray analysis identified some miRNAs differentially regulated by sildenafil, including down-regulation of miR-22-3p, confirmed by real-time quantitative PCR (P < .001). Sildenafil's modulation of miR-22-3p expression was confirmed in vitro in HL1 cardiomyocytes. Up-regulation of SIRT1, a known target of miR-22-3p, was found in both serum and sc fat in sildenafil-treated subjects. Compared with vehicle, 12-week sildenafil treatment down-regulated miR-22-3p and up-regulated Sirtuin1 (SIRT1) gene expression in VAT from db/db mice, shifting adipose tissue cell composition toward a less inflamed profile.Treatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression.CONCLUSIONSTreatment with PDE5i in humans and murine models of diabetes improves VAT, targeting SIRT1 through a modulation of miR-22-3p expression. |
| Author | Giannetta, Elisa Pozza, Carlotta Gianfrilli, Daniele Pofi, Riccardo Galea, Nicola Panio, Giuseppe Sbardella, Emilia Carbone, Iacopo Venneri, Mary A. Isidori, Andrea M. di Dato, Carla Naro, Fabio Lenzi, Andrea Fiore, Daniela |
| AuthorAffiliation | Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy; Department of Radiological, Oncological and Pathological Sciences (N.G., I.C.), Sapienza University of Rome, 00161 Rome, Italy; and Department of Anatomical, Histological, Forensic, and Orthopaedic Sciences (G.P., F.N.), Sapienza University, 00161 Rome, Italy |
| AuthorAffiliation_xml | – name: Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy; Department of Radiological, Oncological and Pathological Sciences (N.G., I.C.), Sapienza University of Rome, 00161 Rome, Italy; and Department of Anatomical, Histological, Forensic, and Orthopaedic Sciences (G.P., F.N.), Sapienza University, 00161 Rome, Italy |
| Author_xml | – sequence: 1 givenname: Daniela surname: Fiore fullname: Fiore, Daniela organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 2 givenname: Daniele surname: Gianfrilli fullname: Gianfrilli, Daniele organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 3 givenname: Elisa surname: Giannetta fullname: Giannetta, Elisa organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 4 givenname: Nicola surname: Galea fullname: Galea, Nicola organization: 2Department of Radiological, Oncological and Pathological Sciences (N.G., I.C.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 5 givenname: Giuseppe surname: Panio fullname: Panio, Giuseppe organization: 3Department of Anatomical, Histological, Forensic, and Orthopaedic Sciences (G.P., F.N.), Sapienza University, 00161 Rome, Italy – sequence: 6 givenname: Carla surname: di Dato fullname: di Dato, Carla organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 7 givenname: Riccardo surname: Pofi fullname: Pofi, Riccardo organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 8 givenname: Carlotta surname: Pozza fullname: Pozza, Carlotta organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 9 givenname: Emilia surname: Sbardella fullname: Sbardella, Emilia organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 10 givenname: Iacopo surname: Carbone fullname: Carbone, Iacopo organization: 2Department of Radiological, Oncological and Pathological Sciences (N.G., I.C.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 11 givenname: Fabio surname: Naro fullname: Naro, Fabio organization: 3Department of Anatomical, Histological, Forensic, and Orthopaedic Sciences (G.P., F.N.), Sapienza University, 00161 Rome, Italy – sequence: 12 givenname: Andrea surname: Lenzi fullname: Lenzi, Andrea organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 13 givenname: Mary A. surname: Venneri fullname: Venneri, Mary A. organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy – sequence: 14 givenname: Andrea M. surname: Isidori fullname: Isidori, Andrea M. email: andrea.isidori@uniroma1.it organization: 1Department of Experimental Medicine (D.F., D.G., E.G., C.d.D., R.P., C.P., E.S., A.L., M.A.V., A.M.I.), Sapienza University of Rome, 00161 Rome, Italy |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26964730$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1ks1r2zAYh8XoWNNut52HYIftMLf6smX1FtJ0CxRW2mzsJmT5daPMtlJJXsh_P6dpL4UKhBA8zyvp_ekEHfW-B4Q-UnJGGSXna3vGCM0zwXL2Bk2oEnkmqZJHaEIIo5mS7M8xOolxTQgVIufv0DErVCEkJxP0cHM5z_GiX7nKJed7PO2gdT6YBBH_dtFCMC2e1m7jo0s7vDThHpLr73FaAe7cbcbY-d3idknxjUmrrdld4Pk_V0NvAV8F3z1ys_nsbnGJl8GZ9j1625g2woen9RT9upovZz-y65_fF7PpdWZFwfKsUFVuK1opym1R1oYDAOe2tDU3ChStK1mWpJGMU6JqYKSoDYPaClPyRhYNP0VfD3U3wT8MEJPu9s9pW9ODH6KmUkpVUk7kiH5-ga79EPrxdprTQnAphVAj9emJGqoOar0JrjNhp5-bOQLsANjgYwzQaOuS2Xc1BeNaTYneJ6bXVu8T0_vERunbC-m57iu4OOBb3yYI8W87bCHoFZg2rTQZhyhkmY1CQcS4y8bJ8lH7ctD8sHntgMcfxP8D4QavxA |
| CitedBy_id | crossref_primary_10_1038_s41573_019_0033_4 crossref_primary_10_5534_wjmh_180026 crossref_primary_10_1093_jsxmed_qdad057 crossref_primary_10_3233_ADR_200166 crossref_primary_10_1042_CS20180487 crossref_primary_10_1016_j_biopha_2018_09_061 crossref_primary_10_3389_fendo_2022_981622 crossref_primary_10_1210_endocr_bqac090 crossref_primary_10_2139_ssrn_3745196 crossref_primary_10_1038_s41598_019_53019_2 crossref_primary_10_1111_andr_12837 crossref_primary_10_1016_j_bbamcr_2022_119362 crossref_primary_10_1016_j_coph_2021_08_007 crossref_primary_10_1080_10495398_2020_1763375 crossref_primary_10_3390_ijms21218244 crossref_primary_10_1096_fj_202000506R crossref_primary_10_2174_0115665240270426231123155924 crossref_primary_10_3390_obesities2030026 crossref_primary_10_1002_jcp_26796 crossref_primary_10_1016_j_metabol_2025_156153 crossref_primary_10_1371_journal_pone_0195528 crossref_primary_10_1186_s12967_022_03581_7 crossref_primary_10_1007_s40618_016_0502_0 crossref_primary_10_1177_20420188241229540 crossref_primary_10_1155_2019_5276096 crossref_primary_10_1016_j_eclinm_2023_101985 crossref_primary_10_1038_s41392_022_01257_8 crossref_primary_10_1126_scitranslmed_abl8503 crossref_primary_10_1113_JP283960 crossref_primary_10_1172_jci_insight_121739 crossref_primary_10_1016_j_numecd_2016_06_001 crossref_primary_10_1155_2020_7078108 crossref_primary_10_1016_j_heliyon_2023_e22487 crossref_primary_10_31083_j_rcm2409251 crossref_primary_10_3233_ADR_200191 crossref_primary_10_1186_s13578_023_01097_1 crossref_primary_10_3389_fendo_2022_1021326 crossref_primary_10_1007_s12020_016_1208_y crossref_primary_10_7554_eLife_68832 crossref_primary_10_1152_ajpheart_00024_2020 crossref_primary_10_1210_jc_2018_02525 crossref_primary_10_1136_bmjdrc_2019_001111 crossref_primary_10_5534_wjmh_200027 crossref_primary_10_1016_j_cellsig_2023_110622 crossref_primary_10_1016_j_gene_2019_144144 crossref_primary_10_1016_j_prostaglandins_2020_106454 crossref_primary_10_1038_srep44584 |
| ContentType | Journal Article |
| Copyright | Copyright © 2016 by the Endocrine Society 2016 Copyright © 2016 by The Endocrine Society Copyright © 2016 by the Endocrine Society |
| Copyright_xml | – notice: Copyright © 2016 by the Endocrine Society 2016 – notice: Copyright © 2016 by The Endocrine Society – notice: Copyright © 2016 by the Endocrine Society |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QP 7T5 7TM H94 K9. 7X8 |
| DOI | 10.1210/jc.2015-4252 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Calcium & Calcified Tissue Abstracts Immunology Abstracts Nucleic Acids Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Immunology Abstracts Calcium & Calcified Tissue Abstracts Nucleic Acids Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE AIDS and Cancer Research Abstracts MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1945-7197 |
| EndPage | 1534 |
| ExternalDocumentID | 26964730 10_1210_jc_2015_4252 00004678-201604000-00025 10.1210/jc.2015-4252 |
| Genre | Randomized Controlled Trial Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- -~X .55 .XZ 08P 0R~ 18M 1TH 29K 2WC 34G 354 39C 4.4 48X 53G 5GY 5RS 5YH 8F7 AABZA AACZT AAIMJ AAPQZ AAPXW AARHZ AAUAY AAVAP AAWTL ABBLC ABDFA ABEJV ABGNP ABJNI ABLJU ABMNT ABNHQ ABOCM ABPMR ABPPZ ABPQP ABPTD ABQNK ABVGC ABWST ABXVV ACGFO ACGFS ACPRK ACUTJ ACYHN ADBBV ADGKP ADGZP ADHKW ADQBN ADRTK ADVEK AELWJ AEMDU AENEX AENZO AETBJ AEWNT AFCHL AFFZL AFGWE AFOFC AFRAH AFXAL AGINJ AGKRT AGQXC AGUTN AHMBA AHMMS AJEEA ALMA_UNASSIGNED_HOLDINGS APIBT ARIXL ASPBG ATGXG AVWKF AZFZN BAWUL BAYMD BCRHZ BEYMZ BSWAC BTRTY C45 CDBKE CS3 D-I DAKXR DIK E3Z EBS EJD EMOBN ENERS F5P FECEO FHSFR FLUFQ FOEOM FOTVD FQBLK GAUVT GJXCC GX1 H13 HZ~ H~9 KBUDW KOP KQ8 KSI KSN L7B M5~ MHKGH MJL N9A NLBLG NOMLY NOYVH NVLIB O9- OAUYM OBH OCB ODMLO OFXIZ OGEVE OHH OJZSN OK1 OPAEJ OVD OVIDX P2P P6G REU ROX ROZ TEORI TJX TLC TR2 TWZ VVN W8F WOQ X7M YBU YFH YHG YOC YSK ZY1 ~02 ~H1 .GJ 3O- 7X7 88E 8FI 8FJ AAJQQ AAKAS AAPGJ AAQQT AAUQX AAWDT AAYJJ ABDPE ABUWG ABXZS ACFRR ACVCV ACZBC ADMTO ADNBA ADZCM AEMQT AEOTA AERZD AFFNX AFFQV AFKRA AFYAG AGMDO AGORE AHGBF AI. AJBYB AJDVS ALXQX APJGH AQDSO AQKUS AVNTJ BENPR BPHCQ BVXVI CCPQU EIHJH FEDTE FYUFA HMCUK HVGLF IAO IHR INH ITC J5H M1P MBLQV N4W NU- OBFPC PHGZM PHGZT PQQKQ PROAC PSQYO TMA UKHRP VH1 WHG X52 ZGI ZXP AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QP 7T5 7TM H94 K9. 7X8 |
| ID | FETCH-LOGICAL-c4625-69b5cb1b913c68da3eee33c8cd3a9e91db7880f723109de206da2edc4a83f76f3 |
| ISSN | 0021-972X 1945-7197 |
| IngestDate | Fri Jul 11 01:58:56 EDT 2025 Mon Jun 30 12:40:58 EDT 2025 Thu Apr 03 06:58:24 EDT 2025 Tue Jul 01 01:10:40 EDT 2025 Thu Apr 24 23:09:10 EDT 2025 Fri May 16 03:43:23 EDT 2025 Fri Feb 07 10:35:29 EST 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Language | English |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c4625-69b5cb1b913c68da3eee33c8cd3a9e91db7880f723109de206da2edc4a83f76f3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 |
| PMID | 26964730 |
| PQID | 3164377449 |
| PQPubID | 2046206 |
| PageCount | 10 |
| ParticipantIDs | proquest_miscellaneous_1777981307 proquest_journals_3164377449 pubmed_primary_26964730 crossref_citationtrail_10_1210_jc_2015_4252 crossref_primary_10_1210_jc_2015_4252 wolterskluwer_health_00004678-201604000-00025 oup_primary_10_1210_jc_2015-4252 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 20160401 2016-April 2016-04-00 |
| PublicationDateYYYYMMDD | 2016-04-01 |
| PublicationDate_xml | – month: 04 year: 2016 text: 20160401 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Washington |
| PublicationTitle | The journal of clinical endocrinology and metabolism |
| PublicationTitleAlternate | J Clin Endocrinol Metab |
| PublicationYear | 2016 |
| Publisher | Oxford University Press Copyright by The Endocrine Society |
| Publisher_xml | – name: Oxford University Press – name: Copyright by The Endocrine Society |
| SSID | ssj0014453 |
| Score | 2.4023156 |
| Snippet | Context:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in... CONTEXT:Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in... Visceral adiposity plays a significant role in cardiovascular risk. PDE5 inhibitors (PDE5i) can improve cardiac function and insulin sensitivity in type 2... |
| SourceID | proquest pubmed crossref wolterskluwer oup |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 1525 |
| SubjectTerms | Adipose tissue Adiposity - drug effects Adiposity - genetics Adult Aged Animal models Animals Biopsy Body fat Cardiomyocytes Cardiovascular diseases Cell culture Cyclic Nucleotide Phosphodiesterases, Type 5 - chemistry Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - physiopathology DNA microarrays Double-Blind Method Flow Cytometry Gene expression Heart Humans Inflammation Magnetic resonance imaging Male Mice Mice, Obese MicroRNAs MicroRNAs - genetics Middle Aged miRNA Obesity, Abdominal - drug therapy Obesity, Abdominal - metabolism Obesity, Abdominal - pathology Phosphodiesterase 5 Inhibitors - pharmacology Placebos Real-Time Polymerase Chain Reaction Sildenafil Sildenafil Citrate - pharmacology SIRT1 protein Sirtuin 1 - genetics Sirtuin 1 - metabolism |
| Title | PDE5 Inhibition Ameliorates Visceral Adiposity Targeting the miR-22/SIRT1 Pathway: Evidence From the CECSID Trial |
| URI | https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00004678-201604000-00025 https://www.ncbi.nlm.nih.gov/pubmed/26964730 https://www.proquest.com/docview/3164377449 https://www.proquest.com/docview/1777981307 |
| Volume | 101 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1tb9MwELbKkBAIId4pDGQk-FSZ1YnzYr5NbWEFDaGtQ_sWJY6jFdoU1lYT_D3-GHdO4riokwZfoiixEyX32Hdn33NHyCtZxNoDzcVEGGdMpJyzNE77DLRVX-WhipSpn3L4KTw4ER9Og9NO57cTtbReZW_Ur628kv-RKlwDuSJL9h8kax8KF-Ac5AtHkDAcryTjz8NRACP8bJqZwCvcfpkh5R7XUr9MlwrXm3r7-dREZv3sTUzUd8OPmk-PmId5UY_HRxOOufrPLlKT_6mpNApWbc09GYwGx-Nhb4Lf5JqzCDIn94SlWeoyX8B0VLYJnuZ6BXCbNQkLETHTOsS3Yrlb9fAeAFuc4zKQQ4F3b5Z6VZm8I3hc2w00XWqxnbqrGTx0gmAadgFnMjIl1kE_VZOyFAGLeBXHa2fttle7JmHmYKzo5OhzmNLFVl0Bzi7qCsxjyQMGc5fX6sQmDuAvVWkDGNF1gv7JV5Vg7wR7XyPXPfBVsIzGcPzRbmUJUadCrT-sZl8gdcp994ZdtMG1dFyeW-T2xQKjKJbfDInCMYUmd8md2oeh-xUg75GOLu-TG4d1lMYD8gNxSVtcUgeXtMEltbikFpcUsEYrXO4ZVNIalW9pg0mKmDTtKkxSg8mH5OTdaDI4YHVpD6YEeNwslFmgMp5J7qswzlNfa-37Kla5n0oteZ5FoFiKCL0PmWuvH-app3Ml0tgvorDwH5GdclHqJ4TmqHhiBW40WKpZWEg_yGTBPS0UL4pAdUmv-bGJqvPeY_mVWbJNiF3y2rb-XuV7uaQdBRld1oRVTXYbASb1UFwmPsed8kgI2SUv7e05_voZRrcv1suER1EkYzAuoy55XAnevsgLkTru97uEbSAhqWjTifH5wQBlOLhQQZu8EV7w9Irf9YzcbIflLtlZna_1czC7V9kLA-s_0WfQKw |
| linkProvider | Flying Publisher |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=PDE5+Inhibition+Ameliorates+Visceral+Adiposity+Targeting+the+miR-22%2FSIRT1+Pathway%3A+Evidence+From+the+CECSID+Trial&rft.jtitle=The+journal+of+clinical+endocrinology+and+metabolism&rft.au=Fiore%2C+Daniela&rft.au=Gianfrilli%2C+Daniele&rft.au=Giannetta%2C+Elisa&rft.au=Galea%2C+Nicola&rft.date=2016-04-01&rft.issn=0021-972X&rft.eissn=1945-7197&rft.volume=101&rft.issue=4&rft.spage=1525&rft.epage=1534&rft_id=info:doi/10.1210%2Fjc.2015-4252&rft.externalDBID=n%2Fa&rft.externalDocID=10_1210_jc_2015_4252 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0021-972X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0021-972X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0021-972X&client=summon |