リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「ステロイドホルモンによる免疫細胞を介した内臓脂肪組織における肥満関連慢性炎症制御機構の解明」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

ステロイドホルモンによる免疫細胞を介した内臓脂肪組織における肥満関連慢性炎症制御機構の解明

石川 明香里 富山大学

2020.09.28

概要

本邦では、生活習慣や社会環境の変化により糖尿病人口が増加し、平成 28 年の調査では約 1,000 万人が糖尿病と推計されている。糖代謝の調節にはインスリンを含む様々なホルモンが関与する。ステロイドホルモンのひとつであるアルドステロンは、鉱質コルチコイド受容体 (MR) を介してインスリン抵抗性を誘導することが知られている。当研究室ではこれまで、MR 阻害薬エプレレノン (Ep) が肥満マウスの糖代謝を改善することを報告してきた。一方、2 型糖尿病の基盤病態であるインスリン抵抗性の進展には、脂肪組織の慢性炎症が深く関わる。したがって、本研究でははじめに、慢性炎症に寄与する主要細胞であるマクロファージ (Mφ) の MR に着目し、Ep による糖代謝改善機構を検討した。

一方、慢性炎症を抑制し、糖代謝恒常性の維持を担う免疫細胞として、制御性 T 細胞 (Treg) の重要性が示されている。女性ホルモンであるエストロゲンは、インスリン標的組織に作用して糖代謝を亢進するほか、Treg の分化を促進することが報告されている。女性では閉経に伴い肥満者および糖尿病患者数が増加するが、閉経に伴う糖代謝異常におけるエストロゲンの脂肪組織 Treg への関与は不明である。そこで次に、閉経肥満マウスを作製し、さらに生理的なエストロゲン補充モデルを確立し、脂肪組織 Treg を介したエストロゲンの抗糖尿病作用を検討した。本研究により、これらステロイドホルモンと免疫細胞の観点から脂肪組織の慢性炎症制御機構を解明することで、糖尿病の新たな治療戦略を探求した。

この論文で使われている画像

参考文献

Amengual-Cladera E, Lladó I, Gianotti M, Proenza AM. Sex differences in the effect of high-fat diet feeding on rat white adipose tissue mitochondrial function and insulin sensitivity. Metabolism 61: 1108-1117, 2012

Araujo-Pires AC, Vieira AE, Francisconi CF, Biguetti CC, Glowacki A, Yoshizawa S, et al. IL-4/CCL22/CCR4 axis controls regulatory T-cell migration that suppresses inflammatory bone loss in murine experimental periodontitis. J Bone Miner Res. 30: 412-422, 2015

Armani A, Cinti F, Marzolla V, Morgan J, Cranston GA, Antelmi A, et al. Mineralocorticoid receptor antagonism induces browning of white adipose tissue through impairment of autophagy and prevents adipocyte dysfunction in high- fat-diet-fed mice. FASEB J. 28: 3745-3757, 2014

Asarian L, Geary N. Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats. Horm Behav. 42: 461-471, 2002

Barish GD, Downes M, Alaynick WA, Yu RT, Ocampo CB, Bookout AL, et al. A nuclear receptor Atlas: macrophage activation. Mol Endocrinol. 19: 2466-2477, 2005

Becker M, Levings MK, Daniel C. Adipose-tissue regulatory T cells: Critical players in adipose-immune crosstalk. Eur J Immunol. 47: 1867-1874, 2017

Bénézech C, Jackson-Jones LH. ILC2 orchestration of local immune function in adipose tissue. Front Immunol. 10: 171, 2019

Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 11: 889-896, 2010

Caprio M, Fève B, Claës A, Viengchareun S, Lombès M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J. 21: 2185-2194, 2007

Caprio M, Antelmi A, Chetrite G, Muscat A, Mammi C, Marzolla V, et al. Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: potential implications for the treatment of metabolic syndrome. Endocrinology 15: 113-125, 2011

Campbell DJ. Control of regulatory T cell migration, function, and homeostasis. J Immunol. 195: 2507-2513, 2015

Cephus JY, Stier MT, Fuseini H, Yung JA, Toki S, Bloodworth MH, et al. Testosterone attenuates group 2 innate lymphoid cell-mediated airway inflammation. Cell Rep. 21: 2487-2499, 2017

Chaudhry A, Rudensky AY. Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest. 123: 939-944, 2013

Chow Z, Banerjee A, Hickey MJ. Controlling the fire−tissue-specific mechanisms of effector regulatory T-cell homing. Immunol Cell Biol. 93: 355-363, 2015

Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486: 549-553, 2012

Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 21: 248-255, 2015

Corry DB, Tuck ML. The effect of aldosterone on glucose metabolism. Curr Hypertens Rep. 5: 106-9, 2003

D’Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS. Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem. 280: 35983-35991, 2005

Do H, Dobrovic A. Sequence artifacts in DNA from formalin-fixed tissues: causes and strategies for minimization. Clin Chem. 61: 64-71, 2015

Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320: 674-677, 2008

Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 60: 2954-2962, 2019

Favre GA, Esnault VL, Van Obberghen E. Modulation of glucose metabolism by the renin-angiotensin-aldosterone system. Am J Physiol Endocrinol Metab. 308: E435-E449, 2015

Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 15: 930-939, 2009

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 4: 330-336, 2003

Fujisaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y, et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58: 2574-2582, 2009

Giacchetti G, Sechi LA, Rilli S, Carey RM. The renin-angiotensin-aldosterone system, glucose metabolism and diabetes. Trends Endocrinol Metab. 16: 120-126, 2005

Guo C, Ricchiuti V, Lian BQ, Yao TM, Coutinho P, Romero JR, et al. Mineralocorticoid receptor blockade reverses obesity- related changes in expression of adiponectin, peroxisome proliferator-activated receptor-gamma, and proinflammatory adipokines. Circulation 117: 2253-2261. 2008

Han JM, Levings MK. Immune regulation in obesity-associated adipose inflammation. J Immunol. 191: 527-532, 2013

Hirata A, Maeda N, Hiuge A, Hibuse T, Fujita K, Okada T, et al. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 84: 164-172, 2009

Ho MF, Bongartz T, Liu M, Kalari KR, Goss PE, Shepherd LE, et al. Estrogen, SNP-dependent chemokine expression and selective estrogen receptor modulator regulation. Mol Endocrinol. 30: 382-398, 2016

Honda H, Nagai Y, Matsunaga T, Okamoto N, Watanabe Y, Tsuneyama K, et al. Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation. J Leukoc Biol. 96: 1087-1100, 2014

Ichihara Y, Wada T, Soeda Y, Ishii Y, Sasahara M, Tsuneki H, et al. SH2-Containing Inositol 5’-phosphatase 2 selectively impairs hypothalamic insulin signalling and regulation of food intake in mice. J Neuroendocrinol. 25: 372–382, 2013

Iwanami J, Mogi M, Okamoto S, Gao XY, Li JM, Min LJ, et al. Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model. Eur J Pharmacol. 566: 153-159, 2007

Kadoya H, Satoh M, Sasaki T, Taniguchi S, Takahashi M, Kashihara N. Excess aldosterone is a critical danger signal for inflammasome activation in the development of renal fibrosis in mice. FASEB J. 29: 3899-3910, 2015

Karvonen-Gutierrez CA, Park SK, Kim C. Diabetes and menopause. Curr Diab Rep. 16: 20, 2016

Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 16: 626-638, 2016

Kolodin D, van Panhuys N, Li C, Magnuson AM, Cipolletta D, Miller CM, et al. Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab. 21: 543-557, 2015

Lackey DE, Olefsky JM. Regulation of metabolism by the innate immune system. Nat Rev Endocrinol. 12: 15-28, 2016

Laffont S, Blanquart E, Savignac M, Cénac C, Laverny G, Metzger D, et al. Androgen signaling negatively controls group 2 innate lymphoid cells. J Exp Med. 214: 1581-1592, 2017

Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 13: 397-411, 2013

Li C, DiSpirito JR, Zemmour D, Spallanzani RG, Kuswanto W, Benoist C, et al. TCR transgenic mice reveal stepwise, multi-site acquisition of the distinctive fat-Treg phenotype. Cell 174: 285-299, 2018

Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 110: 851-860, 2002

Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, et al. Effect of oestrogen plus progestin on the incidence of diabetes in post menopausal women: results from the women’s health initiative hormone trial. Diabetologia 47: 1175-1187, 2004

Marzolla V, Armani A, Zennaro MC, Cinti F, Mammi C, Fabbri A, et al. The role of the mineralocorticoid receptor in adipocyte biology and fat metabolism. Mol Cell Endocrinol. 350: 281-288, 2012

Mazziotti G, Gazzaruso C, Giustina A. Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol Metab. 22: 499-506, 2011

Menéndez E, Valdés S, Botasa P, Delgado E, Abello N. Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study. Endocrinol Nutr. 58: 3-8, 2011

Meziane H, Ouagazzal AM, Aubert L, Wietrzych M, Krezel W. Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies. Genes Brain Behav. 6: 192-200, 2007

Nagira K, Sasaoka T, Wada T, Fukui K, Ikubo M, Hori S, et al. Altered subcellular distribution of estrogen receptor α is implicated in estradiol-induced dual regulation of insulin signaling in 3T3-L1 adipocytes. Endocrinology 147: 1020-1028, 2006

Nishioka T, Suzuki M, Onishi K, Takakura N, Inada H, Yoshida T, et al. Eplerenone attenuates myocardial fibrosis in the angiotensin II-induced hypertensive mouse: involvement of tenascin-C induced by aldosterone-mediated inflammation. J Cardiovasc Pharmacol. 49: 261-268, 2007

Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 15: 914-920, 2009

Ogawa S, Lozach J, Benner C, Pascual G, Tangirala RK, Westin S, et al. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 122: 707-721, 2005

Ohkura N, Kitagawa Y, Sakaguchi S. Development and maintenance of regulatory T cells. Immunity 38: 414-423, 2013

Olivares-Reyes JA, Arellano-Plancarte A, Castillo-Hernandez JR. Angiotensin 2 and the development of insulin resistance: implications for diabetes. Mol Cell Endocrinol. 302: 128-139, 2009

Onogi Y, Wada T, Kamiya C, Inata K, Matsuzawa T, Inaba Y, et al. PDGFRβ regulates adipose tissue expansion and glucose metabolism via vascular remodeling in diet-induced obesity. Diabetes 66: 1008-1021, 2017

Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol. 402: 113-119, 2015

Pettersson US, Waldén TB, Carlsson PO, Jansson L, Phillipson M. Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One 7: e46057, 2012

Pisani DF, Beranger GE, Corinus A, Giroud M, Ghandour RA, Altirriba J, et al. The K+ channel TASK1 modulates beta-adrenergic response in brown adipose tissue through the mineralocorticoid receptor pathway. FASEB J. 30: 909-922, 2016

Poehlein CH, Haley DP, Walker EB, Fox BA. Depletion of tumor-induced Treg prior to reconstitution rescues enhanced priming of tumor-specific, therapeutic effector T cells in lymphopenic hosts. Eur J Immunol. 39: 3121-3133, 2009

Polanczyk MJ, Hopke C, Huan J, Vandenbark AA, Offner H. Enhanced FoxP3 expression and Treg cell function in pregnant andestrogen-treated mice. J Neuroimmunol. 170: 85-92, 2005

Ribas V, Drew BG, Le JA, Soleymani T, Daraei P, Sitz D, et al. Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proc Natl Acad Sci U S A. 108: 16457-16462, 2011

Rocha VZ, Folco EJ, Ozdemir C, Sheikine Y, Christen T, Sukhova GK, et al. CXCR3 controls T-cell accumulation in fat inflammation. Arterioscler Thromb Vasc Biol. 34: 1374-1381, 2014

Sameshima A, Wada T, Ito T, Kashimura A, Sawakawa K, Yonezawa R, et al. Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity. J Endocrinol. 227: 25-36, 2015

Stienstra R, Joosten LA, Koenen T, van Tits B, van Diepen JA, van den Berg SA, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 12: 593-605, 2010

Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 108: 15324-15329, 2011

Schiller NK, Black AS, Bradshaw GP, Bonnet DJ, Curtiss LK. Participation of macrophages in atherosclerotic lesion morphology in LDLr-/- mice. J Lipid Res. 45: 1398-1409, 2004

Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, et al. 17β-estradiol directly lowers mitochondrial membrane microviscosity and improves bioenergetic function in skeletal muscle. Cell Metab. 27: 167-179, 2018

Travers RL, Motta AC, Betts JA, Bouloumié A, Thompson D. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obes. 39: 762-769, 2015

Urbanet R, Nguyen DCA, Feraco A, Venteclef N, El Mogrhabi S, Sierra- Ramos C, et al. Adipocyte mineralocorticoid receptor activation leads to metabolic syndrome and induction of prostaglandin D2 synthase. Hypertension 66: 149-157, 2015

Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schütz G, et al. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest. 120: 3350-3364, 2010

Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 17: 179-188, 2011

Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Med. 16: 276-285, 2015

Wada T, Ishikawa A, Watanabe E, Nakamura Y, Aruga Y, Hasegawa H, et al. Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance. J Endocrinol. 235: 179-191, 2017

Wada T, Kenmochi H, Miyashita Y, Sasaki M, Ojima M, Sasahara M, et al. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high- fructose diet. Endocrinology 151: 2040-2049, 2010

Wada T, Miyashita Y, Sasaki M, Aruga Y, Nakamura Y, Ishii Y, et al. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet. Am J Physiol Endocrinol Metab. 305: E1415-E1425, 2013

Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T. Aldosterone inhibits insulin -induced glucose uptake by degradation of insulin receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. Endocrinology 150: 1662-1669, 2009

Wei S, Kryczek I, Zou W. Regulatory T-cell compartmentalization and trafficking. Blood 108: 426-431, 2006

Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, et al. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med. 15: 921-929, 2009

Wolowczuk I, Hennart B, Leloire A, Bessede A, Soichot M, Taront S, et al. Poulain-Godefroy, Tryptophan metabolism activation by indoleamine 2,3-dioxygenase in adipose tissue of obese women: an attempt to maintain immune homeostasis and vascular tone. Am J Physiol Regul Integr Comp Physiol. 303: R135-R143, 2012

Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 14: 453-465, 2011

Yamada Y, Okubo Y, Shimada A, Oikawa Y, Yamada S, Narumi S, et al. Acceleration of diabetes development in CXC chemokine receptor 3 (CXCR3)-deficient NOD mice. Diabetologia 55: 2238-2245, 2012

Yamazaki T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, et al. CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol. 181: 8391-8491, 2008

Yonezawa R, Wada T, Matsumoto N, Morita M, Sawakawa K, Ishii Y, et al. Central versus peripheral impact of estradiol on the impaired glucose metabolism in ovariectomized mice on a high-fat diet. Am J Physiol Endocrinol Metab. 303: E445-E456, 2012

Zeng Q, Sun X, Xiao L, Xie Z, Bettini M, Deng T. A unique population: adipose-resident regulatory T cells. Front Immunol. 9: 2075, 2018

Zeyda M, Huber J, Prager G, Stulnig TM. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity 19: 743-748, 2011

Zhang YY, Li C, Yao GF, Du LJ, Liu Y, Zheng XJ, et al. Deletion of macrophage mineralocorticoid receptor protects hepatic steatosis and insulin resistance through ERa/HGF/Met pathway. Diabetes 66: 1535-1547, 2017"

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る