Role of ectopic fat in the mechanism of cardiovascular diseases

• Project/Area Number: 23591314
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokushima
• Principal Investigator: SHIMABUKURO Michio 徳島大学, ヘルスバイオサイエンス研究部, 特任教授 (60271144)
• Co-Investigator(Kenkyū-buntansha): MASUZAKI Hiroaki 琉球大学, 医学(系)研究科(研究院), 教授 (00291899) ; KARIYA Kenichi 琉球大学, 医学(系)研究科(研究院), 教授 (40263371)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遊離脂肪酸 / 内臓肥満症 / 異所性脂肪 / 糖尿病 / インスリン抵抗性

Research Abstract

1. Fat contents in the abdomen, liver, skeletal muscle and epicardium were measured; 2. Expression of molecules in the endothelium was quantified by 2D SDS-PAGE and RT-PCR. Activation of caspase-3/7 was observed ~12 hours after treated with palmitate 200 micromol/L, and the activation was reduced by a knockdown of molecule X; 3. Epicardial adipose tissue volume (EATV), cytokine/adipocytokine profiles in epicardial adipose tissue were strongly associated in human samples.

Research Products

• [Journal Article] Effects of brown rice diet on visceral obesity and endothelial function: the BRAVO study. (2014)
  • Author(s): 1. Shimabukuro M, Higa M, Kinjo R, Yamakawa K, Tanaka H, Kozuka C, Yabiku K, Taira S, Sata M, Masuzaki H.
  • Journal Title: Br J Nutr Volume: 111 Issue: 2 Pages: 310-320
  • DOI: 10.1017/s0007114513002432
  • Peer Reviewed
• [Journal Article] Azilsartan, an angiotensin II type 1 receptor blocker, restores endothelial function by reducing vascular inflammation and by increasing the phosphorylation ratio Ser1177/Thr497 of endothelial nitric oxide synthase in diabetic mice. (2014)
  • Author(s): Matsumoto S, Shimabukuro M, Fukuda D, Soeki T, Yamakawa K, Masuzaki H, Sata M.
  • Journal Title: Cardiovasc Diabetol Volume: 13 Issue: 1 Pages: 30-30
  • DOI: 10.1186/1475-2840-13-30
  • Peer Reviewed / Open Access
• [Journal Article] Association of lower limb muscle mass and energy expenditure with visceral fat mass in healthy men (2014)
  • Author(s): Yagi S, Kadota M, Aihara K, Nishikawa K, Hara T, Ise T, Ueda Y, Iwase T, Akaike M, Shimabukuro M, Katoh S, Sata M.
  • Journal Title: Diabetology & metabolic syndrome Volume: 6 Issue: 1 Pages: 27-27
  • DOI: 10.1186/1758-5996-6-27
  • Peer Reviewed / Open Access
• [Journal Article] Association of borderline ankle-brachial index with mortality and the incidence of peripheral artery disease in diabetic patients. (2014)
  • Author(s): Natsuaki C, Inoguchi T, Maeda Y, Yamada T, Sasaki S, Sonoda N, Shimabukuro M, Nawata H, Takayanagi R.
  • Journal Title: Atherosclerosis Volume: 234 Issue: 2 Pages: 360-365
  • DOI: 10.1016/j.atherosclerosis.2014.03.018
  • Peer Reviewed
• [Journal Article] Miglitol,α-glycosidase inhibitor, reduces visceral fat accumulation and cardiovascular risk factors in subjects with the metabolic syndrome (2013)
  • Author(s): Shimabukuro M, et al
  • Journal Title: Int J Cardiol Volume: 167 Issue: 5 Pages: 2108-2113
  • DOI: 10.1016/j.ijcard.2012.05.109
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury (2013)
  • Author(s): Y. Hirata, H. Kurobe, C. Nishio, K. Tanaka, D. Fukuda, E. Uematsu, S. Nishimoto, T. Soeki, N. Harada, H. Sakaue, T. Kitagawa, M. Shimabukuro, N. Nakaya, M. Sata
  • Journal Title: Eur. J. Pharmacol. Volume: 699 Issue: 1-3 Pages: 106-111
  • DOI: 10.1016/j.ejphar.2012.11.057
  • Peer Reviewed
• [Journal Article] Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model (2013)
  • Author(s): Y. Hirata, H. Kurobe, E. Uematsu, S. Yagi, T. Soeki, H. Yamada, D. Fukuda, M. Shimabukuro, M. Nakayama, K. Matsumoto, Y. Sakai, T. Kitagawa, M. Sata
  • Journal Title: Eur. J. Pharmacol. Volume: 699 Issue: 1-3 Pages: 81-87
  • DOI: 10.1016/j.ejphar.2012.11.045
  • Peer Reviewed
• [Journal Article] Lipid Deposition in Various Sites of the Skeletal Muscles and Liver Exhibits a Positive Correlation with Visceral Fat Accumulation in Middle-aged Japanese Men with Metabolic Syndrome (2013)
  • Author(s): Taira S, et al
  • Journal Title: Internal Medicine Volume: 52 Issue: 14 Pages: 1561-1571
  • DOI: 10.2169/internalmedicine.52.0521
  • NAID: 130003365715
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Perivascular adipose tissue-secreted angiopoietin-like protein2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury. (2013)
  • Author(s): Tian Z, Miyata K, Tazume H, Sakauguchi H, Kadomatsu T, Horio E, Takahashi O, Komohara Y, Araki K, Hirata Y, Tabata M, Takanashi S, Takeya M, Hao H, Shimabukuro M, Sata M, Kawasuji M, Oike Y.
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 1-12
  • DOI: 10.1016/j.yjmcc.2013.01.004
  • Peer Reviewed
• [Journal Article] Defects of vascular nitric oxide bioavailability in subjects with impaired glucose tolerance: A potential link to insulin resistance. (2013)
  • Author(s): Michio Shimabukuro
  • Journal Title: International Journal of Cardiology Volume: in press Issue: 1 Pages: 298-300
  • DOI: 10.1016/j.ijcard.2012.09.194
  • Peer Reviewed
• [Journal Article] Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis (2013)
  • Author(s): M. Shimabukuro, Y. Hirata, M. Tabata, M. Dagvasumberel, H. Sato, H. Kurobe, D. Fukuda, T. Soeki, T. Kitagawa, S. Takanashi, M. Sata
  • Journal Title: Arterioscler. Thromb. Vasc. Biol. Volume: 33 Issue: 5 Pages: 1077-1084
  • DOI: 10.1161/atvbaha.112.300829
  • Peer Reviewed
• [Journal Article] Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein (2013)
  • Author(s): Soeki T, Niki T, Uematsu E, Bando S, Matsuura T, Kusunose K, Ise T, Ueda Y, Tomita N, Yamaguchi K, Koshiba K, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Akaike M, Shimabukuro M, Kishimoto I, Kangawa K, Sata M
  • Journal Title: Heart Vessels Volume: 28 Issue: 6 Pages: 795-801
  • DOI: 10.1007/s00380-013-0333-2
  • Peer Reviewed
• [Journal Article] Protective effects of selective mineralocorticoid receptor antagonist against aortic aneurysm progression in a novel murine model. (2013)
  • Author(s): Kurobe H, Hirata Y, Matsuoka Y, Sugasawa N, Higashida M, Nakayama T, Maxfield MW, Yoshida Y, Shimabukuro M, Kitagawa T, Sata M.
  • Journal Title: J Surg Res Volume: 185 Issue: 1 Pages: 455-462
  • DOI: 10.1016/j.jss.2013.05.002
  • Peer Reviewed
• [Journal Article] Role of macrophage-derived hypoxia-inducible factor (HIF)-1α as a mediator of vascular remodelling (2013)
  • Author(s): Nakayama T, Kurobe H, Sugasawa N, Kinoshita H, Higashida M, Matsuoka Y, Yoshida Y, Hirata Y, Sakata M, Maxfield M, Shimabukuro M, Takahama Y, Sata M, Tamaki T, Kitagawa T, Tomita S.
  • Journal Title: Cardiovasc Res Volume: 99 Issue: 4 Pages: 705-715
  • DOI: 10.1093/cvr/cvt146
  • Peer Reviewed
• [Journal Article] Pentraxin 3 is a local inflammatory marker in atrial fibrillation (2013)
  • Author(s): Soeki T, Bando S, Uematsu E, Matsuura T, Niki T, Ise T, Kusunose K, Hotchi J, Ueda Y, Tomita N, Yamaguchi K, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Shimabukuro M, Sata M.
  • Journal Title: Heart Vessels Volume: - Issue: 5 Pages: 27-27
  • DOI: 10.1007/s00380-013-0400-8
  • Peer Reviewed / Open Access
• [Journal Article] HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9 (2013)
  • Author(s): Y. Hirata, H. Kurobe, M. Higashida, D. Fukuda, M. Shimabukuro, Y. Higashikuni, T. Kitagawa, M. Sata
  • Journal Title: Atherosclerosis Volume: 231 Issue: 2 Pages: 227-233
  • DOI: 10.1016/j.atherosclerosis.2013.09.010
  • Peer Reviewed
• [Journal Article] Lipid deposition in various sites of skeletal muscle and liver shows correlation with visceral fat accumulation in male patients with metabolic syndrome. (2013)
  • Author(s): Taira S, Shimabukuro M, Higa M, Yabiku K, Kozuka C, Ueda R, Sunagawa S, Ohshiro Y, Doi M, Nanba T, Kawamoto E, Nakayama Y, Nakamura H, Iha T, Nakachi S, Tomoyose T, Ikema T, Yamakawa K, Masuzaki H.
  • Journal Title: Intern Med Volume: 52 Pages: 1561-1571
  • Peer Reviewed
• [Journal Article] Ectopic fat deposition and global cardiometabolic risk: New paradigm in cardiovascular medicine. (2013)
  • Author(s): Shimabukuro M et al.
  • Journal Title: J Med Invest. Volume: 60 Pages: 1-14
  • NAID: 130004465276
  • Peer Reviewed
• [Journal Article] Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. (2013)
  • Author(s): Shimabukuro M et al.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 33 Pages: 1077-1084
  • Peer Reviewed
• [Journal Article] Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury. (2013)
  • Author(s): Tian Z et al.
  • Journal Title: J Mol Cell Cardiol. Volume: 57 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury. (2013)
  • Author(s): Hirata Y et al.
  • Journal Title: Eur J Pharmacol. Volume: 699(1-3) Pages: 106-11
  • Peer Reviewed
• [Journal Article] The Radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation (2012)
  • Author(s): Y. Watanabe, T. Nakamura, S. Ishikawa, S. Fujisaka, I. Usui, K. Tsuneyama, Y. Ichihara, T. Wada, Y. Hirata, T. Suganami, H. Izaki, S. Akira, K. Miyake, H. Kanayama, M. Shimabukuro, M. Sata, T. Sasaoka, Y. Ogawa, K. Tobe, K. Takatsu, Y. Nagai
  • Journal Title: Diabetes Volume: 61 Issue: 5 Pages: 1199-1209
  • DOI: 10.2337/db11-1182
  • Peer Reviewed
• [Journal Article] Brown Rice and Its Component, γ-Oryzanol, Attenuate the Preference for High-Fat Diet by Decreasing Hypothalamic Endoplasmic Reticulum Stress in Mice (2012)
  • Author(s): Kozuka C, Oyadomari S
  • Journal Title: Diabetes Volume: 61 Issue: 12 Pages: 3084-93
  • DOI: 10.2337/db11-1767
  • Peer Reviewed
• [Journal Article] Activation of AMPK-Sirt1 pathway by telmisartan in white adipose tissue: A possible link to anti-metabolic effects (2012)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Sakaue H, Nakaya Y, Masuzaki H, Sata M
  • Journal Title: Eur J Pharmacol Volume: 692 Issue: 1-3 Pages: 84-90
  • DOI: 10.1016/j.ejphar.2012.07.026
  • Peer Reviewed
• [Journal Article] Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects (2012)
  • Author(s): Dagvasumberel M, Shimabukuro M, Nishiuchi T, Ueno J, Takao S, Fukuda D, Hirata Y, Kurobe H, Soeki T, Iwase T, Kusunose K, Niki T, Yamaguchi K, Taketani Y, Yagi S, Tomita N, Yamada H, Wakatsuki T, Harada M, Kitagawa T, Sata M
  • Journal Title: Cardiovasc Diabetol Volume: 11 Issue: 1 Pages: 106-106
  • DOI: 10.1186/1475-2840-11-106
  • Peer Reviewed
• [Journal Article] Eicosapentaenoic acid supplementation changes fatty acid composition and corrects endothelial dysfunction in hyperlipidemic patients. (2012)
  • Author(s): Ken Yamakawa
  • Journal Title: Cardiology Research and Practice Volume: 2012 Pages: 754181-754181
  • DOI: 10.1155/2012/754181
  • Peer Reviewed
• [Journal Article] Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice (2012)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Maeda N, Sakaue H, Masuzaki H, Shimomura I, Sata M.
  • Journal Title: Cardiovascular Diabetol. Volume: 11 Issue: 1 Pages: 139-139
  • DOI: 10.1186/1475-2840-11-139
  • Peer Reviewed
• [Journal Article] Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. (2012)
  • Author(s): Shiota A et al.
  • Journal Title: Cardiovasc Diabetol. Volume: 11 Pages: 139-139
  • Peer Reviewed
• [Journal Article] Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: a 3-dimensional cardiac computed tomography imaging study in Japanese subjects. (2012)
  • Author(s): Dagvasumberel M et al.
  • Journal Title: Cardiovasc Diabetol. Volume: 11 Pages: 106-106
  • Peer Reviewed
• [Journal Article] The Radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation. (2012)
  • Author(s): Watanabe Y
  • Journal Title: Diabetes Volume: 61 Pages: 1199-1209
  • Peer Reviewed
• [Journal Article] A synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury. (2012)
  • Author(s): Hirata Y
  • Journal Title: Eur J Pharmacol Volume: 674 Pages: 352-358
  • Peer Reviewed
• [Journal Article] Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients of type 2 diabetes mellitus (2011)
  • Author(s): Shimabukuro M, et al
  • Journal Title: Diabetic Med Volume: 28 Issue: 7 Pages: 856-864
  • DOI: 10.1111/j.1464-5491.2011.03240.x
  • Peer Reviewed
• [Journal Article] Impaired glucose tolerance, but not impaired fasting glucose, underlies left ventricular diastolic dysfunction (2011)
  • Author(s): Shimabukuro M, et al
  • Journal Title: Diabetes Care Volume: 34 Issue: 3 Pages: 686-690
  • DOI: 10.2337/dc10-1141
  • Peer Reviewed
• [Journal Article] Serum Levels of B-Cell Activating Factor of TNF Family (BAFF) as a Useful Indicator for the Activity of Graves'Disease (2011)
  • Author(s): Sunagawa S, et al
  • Journal Title: J Endocrinol Metab Volume: 1 Pages: 73-78
  • Peer Reviewed
• [Journal Article] A synthetic prostacycline agonist, ONO-1301, ameliorates ventricular remodeling after acute myocardial infarction via up-regulation of HGF in rat (2011)
  • Author(s): Hirata Y, et al
  • Journal Title: Biomed Aging Pathol Volume: 90-96 Pages: 1-1
  • Peer Reviewed
• [Journal Article] A synthetic prostacycline agonist, ONO-1301, ameliorates ventricular remodeling after acute myocardial infarction via up-regulation of HGF in rat (2011)
  • Author(s): Hirata Y
  • Journal Title: Biomed Aging Pathol Volume: 1 Pages: 90-96
• [Journal Article] Impaired glucose tolerance, but not impaired fasting glucose, underlies left ventricular diastolic dysfunction. (2011)
  • Author(s): Shimabukuro M
  • Journal Title: Diabetes Care Volume: 34
• [Presentation] Post-Transcriptional Regulation of Adiponectin by Micro-RNA 378 in Human Visceral and Subcutaneous Adipose Tissue (2013)
  • Author(s): Ishida M
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: Dallas Convention Center(Dallas, USA) (一般演題)
• [Presentation] Macrophage Toll-like Receptor 9 Signaling Contributes to the Development of Insulin Resistance through the Promotion of Inflammation in Adipose Tissue (2013)
  • Author(s): Nishimoto S
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: Dallas Convention Center(Dallas, USA) (一般演題)
• [Presentation] Rivaroxaban, A Novel Oral Anticoagulant, Attenuates Plaque Progression in ApoE-Deficient Mice Through the Inhibition of Pro-Inflammatory Activation of Macrophages (2013)
  • Author(s): Hara T
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: Dallas Convention Center(Dallas, USA) (一般演題)
• [Presentation] Macrophage-Specific Hypoxia-Inducible Factor (HIF)-1α-Deficient Mice Suppress the Vascular Remodeling and Regulate M2 Macrophage Polarization (2013)
  • Author(s): Nakayama T
  • Organizer: AHA Scientific Sessions 2013
  • Place of Presentation: Dallas Convention Center(Dallas, USA) (一般演題)
• [Presentation] Cardiospecific microRNA plasma levels are associated with coronary plaque vulnerability (2013)
  • Author(s): Soeki T
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] MicroRNA miR-378 regulates adipocytokine fate by targeting transcriptional factors in human visceral and subctaneous adipose tissue (2013)
  • Author(s): Ishida M
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] MicroRNA-100 regulates a cluster of adipocytokine expression : A human biopsy study in subcutaneous and visceral adipose tissue (2013)
  • Author(s): Ishida M
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Genetic ablation of TLR9 improves insulin resistance through macrophage accumulation in adipose tissue (2013)
  • Author(s): Nishimoto S
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Visceral fat mass is associated with daily physical activity, leg skeletal muscle mass and fiber intake in healthy men (2013)
  • Author(s): Nishikawa K
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Electrophysiological correlation and prognostic impact of pentraxin 3 as a local inflammatory marker in atrial fibrillation (2013)
  • Author(s): Soeki T
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Ghrelin ameliorates the progression of experimental autoimmune myocarditis (2013)
  • Author(s): Bando S
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Gender-based risk stratification of coronary artery disease in asymptomatic diabetic subjects : a multi-clinic study using multi-detector computed tomography (2013)
  • Author(s): Shimabukuro M, Saito T, Higa T, Nkamura K, Sata M
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)
• [Presentation] Plasma Brain Natriuretic Peptide (BNP) level is elevated in patients with cancer (2013)
  • Author(s): Bando S
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam RAI Exhibition and Convention Centre (Amsterdam, Netherlands)(一般演題)