{"created":"2024-04-18T04:29:17.341220+00:00","id":2000177,"links":{},"metadata":{"_buckets":{"deposit":"6e100a46-5271-48a0-a80d-9447cb195d55"},"_deposit":{"created_by":12,"id":"2000177","owner":"12","owners":[12],"pid":{"revision_id":0,"type":"depid","value":"2000177"},"status":"published"},"_oai":{"id":"oai:obihiro.repo.nii.ac.jp:02000177","sets":["6:8"]},"author_link":[],"item_3_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"ブタ脂肪細胞の褐⾊化に関する外因性刺激および分⼦機構の解明","subitem_alternative_title_language":"ja"}]},"item_3_date_granted_12":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-03-19"}]},"item_3_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"帯広畜産大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10105","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_3_degree_name_9":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（農学）","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Agriculture","subitem_degreename_language":"en"}]},"item_3_description_11":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"2023","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_3_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The beige adipocyte is transformed from white adipocyte with adrenergic stimulation,for example, cold exposure, burn injuries, thyroid hormones, and catecholamine preparations.The transition from white adipocytes to beige adipocytes (browning) alters their metabolicfunctions, influencing physiological functions in both animals and humans. The browning was focused on human health care and it expected to serve as a new therapy for metabolic diseases such as obesity, diabetes mellitus, and dyslipidemia. However, the molecular mechanism of browning is not clearly understood.\nThe study of browning has been performed mainly in human or mouse fat tissues and on culture cell lines, such as 3T3-L1, derived from mouse embryonic cells. As ethical issues are posed by the use of human samples, it is difficult to use them for experiments on browning. Furthermore, previous study observed that different expressions between in vivo and in vitro conditions, and reported the result in experiments of adipocyte depend on the animal species. On the other hand, primary cultures of adipocyte can be immensely beneficial for the investigation of adipocyte functions. Therefore, other animal models and primary cultures can be applied to study browning to obtain insights on human metabolic diseases.\nPig shares similar features with human in terms of anatomy, genetics and physiology, making it a valuable animal model for human research. Previous studies have been reported to genetic similarity between pig and human with genome-wide sequencing of various tissues. In addition, the pig lacks functional UCP1 which is related to browning, so pigs are sensitive to cold environment as domesticated animals. This study specifically targeted the Mangalica Pig, a traditional breed in Hungary with unique physiology and characteristics as a lard-type pig. Mangalica has cold tolerance and can live in a grazing environment year2 round. However, it remains unclear whether white adipocytes undergo browning in response to seasonal changes in Mangalica, and the molecular mechanisms by which Mangalica acquires cold tolerance are yet to be revealed.\nIn this study, I conducted experiments to understand the molecular mechanisms of fat browning. At the cellular level (in vitro), I induced browning in adipocytes using primary cultures from a commercial pig breed's fat tissue. At the in vivo level, experiments with Mangalica were carried out to explore cold stimulation in thermogenic physiology, focusing on muscle and fat tissues. The goal was to achieve a comprehensive understanding of the browning process. In the cellular experiment, the administration of 1 μM isoproterenol to pig fat primary cultures significantly increased the gene expression of PGC-1α and UCP3, which are associated with browning, as well as the COX family genes related to mitochondrial function. Additionally, 1 μM isoproterenol upregulated lipolysis, leading to a significant decrease in the size of lipid droplets and lipid particle content. These results revealed browning in white adipocytes of pigs lacking UCP1. In the in vivo experiment, there was a distinct developmental pattern in fat tissue between Mangalica and a commercial pig breed. The muscle of Mangalica increased the gene expression of ATP2A1 and SLN, and the fat tissue increased the gene expression of PGC-1α, UCP1, UCP2, and UCP3 in winter compered to summer. The genes upregulated in the fat tissue of Mangalica were consistent\nwith the browning observed in pig fat primary culture. These findings suggest that the fat tissue of Mangalica undergoes browning in winter, contributing to its cold tolerance.\nThis study is the first study that demonstrate fat browning using fat primary culture from pig, shedding light on the potential for browning in the fat tissue of Mangalica. These findings offer valuable insights into the mechanism of browning in white adipocytes and hold promise for contributing to the therapeutic interventions for human obesity.","subitem_description_language":"en","subitem_description_type":"Abstract"},{"subitem_description":"⽩⾊脂肪細胞は、寒冷刺激、⽕傷、甲状腺ホルモン刺激、およびアドレナリン作動性のカテコラミンなどの神経刺激によって代謝機能を亢進したベージュ脂肪細胞へと変化（褐⾊化）する。⽩⾊脂肪細胞の褐⾊化に関連するUCP1 は、主要な熱産⽣のタンパク質として考えられており、β3 アドレナリン受容体によるシグナル伝達によって活性化される転写因⼦であるPGC-1α や、PRDM16 などによって発現が促進される。またUCP1タンパク質は、脂肪酸を利⽤し、ミトコンドリアの電⼦伝達系にて脱共役作⽤により熱を産⽣する。したがって、褐⾊化は、⽩⾊脂肪細胞の代謝機能を⼤きく変え、哺乳動物およびヒトの⽣理機能に影響を与え、肥満などの代謝疾患に関する新たな治療⽅法として着⽬されている。褐⾊化研究は、ヒトまたはマウスの脂肪組織およびマウス受精卵から樹⽴した3T3-L1 などの培養細胞株が主に使⽤されている。ヒト脂肪組織を⽤いた褐⾊化の研究は、ヒトの組織を使うという点に倫理的な問題が存在し、マウスの脂肪組織はインスリンの感受性がヒトと⼤きく異なるなど問題点が含まれている。さらに、以前の研究では、⽣体内（in vivo）と培養条件下（in vitro）で異なる実験結果が⽰されるなど、脂肪細胞の褐⾊化において⼀致した⾒解が得られていない。⼀⽅で、初代培養は、⽣体内に⽣理機能に近く、脂肪細胞の機能メカニズムを調べるために⾮常に有益ある。したがって、マウス以外の動物モデルの作製と初代培養の利⽤は、ヒトの代謝疾患に関する洞察を得るため利⽤でき、より⽣体に近いモデルとして期待されている。\nブタは、ヒトと解剖学的、遺伝学的および⽣理学的に類似しており、ヒトの⽣理機能研究において有益な動物モデルとして期待されている。ブタゲノム全体のシーケンシング結果は、ヒトの様々な組織における遺伝⼦群の発現パターンに最も類似であることが報告されている。また、ブタは機能的なUCP1 が⽋損しており、寒冷環境に不耐性という特徴をもつ家畜である。そこで、本研究はハンガリーの伝統的な品種であるマンガリッツァブタに焦点を当て、研究を⾏なった。マンガリッツァはラードタイプのブタとして知られており、特徴的な⽣理機能を持っている。また、マンガリッツァは寒冷耐性を有し、⼀年を通じて放牧飼養が可能である。しかしながら、マンガリッツァが耐寒性を獲得する分⼦メカニズムは不明であり、⽩⾊脂肪細胞が季節の変化に応じて褐⾊化するかどうかはほとんど解明されていない。\n本研究では、脂肪の褐⾊化の分⼦メカニズムを明らかにするために細胞（in vitro）および⽣体（in vivo）レベルで⽣理学研究を⾏った。まずin vitro レベルでは、商業⽤品種のブタの脂肪組織から得た初代培養を使⽤し、脂肪細胞の褐⾊化を誘導した。in vivo レベルでは、実際にマンガリッツァを⽤いて、筋⾁および脂肪組織に焦点を当て、寒冷刺激による⽣理機能の変化を調べた。脂肪の初代培養を⽤いた培養実験では、1 μM のイソプロテレノールを投与することで、PGC-1α、UCP3 およびミトコンドリア機能に関連するCOX ファミリー遺伝⼦の発現が有意に増加した。さらに、1 μM のイソプロテレノールは、脂肪滴のサイズを有意に減少させ、細分化を誘導した。これらの結果は、UCP1を⽋いたブタの⽩⾊脂肪細胞においても褐⾊化を誘導できることを明らかにした。マンガリッツァを⽤いた⽣体実験では、成⻑に伴うマンガリッツァ特異的な脂肪組織の発達の違いを明らかにした。さらに、マンガリッツァは、冬季において筋⾁中のATP2A1 およびSLN の遺伝⼦発現、脂肪中のPGC-1α、UCP1、UCP2、およびUCP3 の遺伝⼦発現が夏に⽐べて有意に増加し、⾮ふるえ熱産⽣による体温の上昇を⽰した。これらの結果は、ブタ脂肪初代培養で観察された褐⾊化時の遺伝⼦の発現動態と⼀致した。したがって、マンガリッツァの脂肪組織は、冬季に褐⾊化し、耐寒性を獲得している可能性を⽰唆した。\nこの研究は、ブタの脂肪初代培養を⽤いて脂肪の褐⾊化を初めて実証した。また、マンガリッツァの脂肪組織が冬季にベージュ脂肪細胞へ機能変化する可能性を⽰し、耐寒性を獲得されるメカニズムを明らかにした。本研究は、⽩⾊脂肪細胞における褐⾊化のメカニズムに関する貴重な知⾒を提供し、ヒトの代謝疾患の解明に資する基礎研究となった。","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_3_description_8":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"博士学位論文","subitem_description_language":"ja","subitem_description_type":"Other"},{"subitem_description":"大学院畜産学研究科 畜産科学専攻","subitem_description_language":"ja","subitem_description_type":"Other"},{"subitem_description":"Doctoral Program of Animal Science and Agriculture","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_3_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第139号"}]},"item_3_publisher_5":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"帯広畜産大学","subitem_publisher_language":"ja"}]},"item_3_rights_14":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"KIM Sangwoo","subitem_rights_language":"en"}]},"item_3_subject_20":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"645","subitem_subject_language":"ja","subitem_subject_scheme":"NDC"}]},"item_3_version_type_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kim, Sangwoo","creatorNameLang":"en"},{"creatorName":"金, 翔宇","creatorNameLang":"ja"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-04-18"}],"filename":"Kim.pdf","filesize":[{"value":"8.9 MB"}],"format":"application/pdf","url":{"label":"全文　Full text","objectType":"fulltext","url":"https://obihiro.repo.nii.ac.jp/record/2000177/files/Kim.pdf"},"version_id":"225c935e-ebd0-49f2-970f-819314b52538"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-04-18"}],"filename":"Abstract(Kim).pdf","filesize":[{"value":"103 KB"}],"format":"application/pdf","url":{"label":"全文の要旨　Abstract","url":"https://obihiro.repo.nii.ac.jp/record/2000177/files/Abstract(Kim).pdf"},"version_id":"8e41bc1f-eab0-42ce-a109-c0d516134565"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-04-18"}],"filename":"Evaluation(Kim).pdf","filesize":[{"value":"204 KB"}],"format":"application/pdf","url":{"label":"審査の要旨　Evaluation","url":"https://obihiro.repo.nii.ac.jp/record/2000177/files/Evaluation(Kim).pdf"},"version_id":"98011687-6593-43bd-978c-d0c8ad47a8fc"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Elucidating Exogenous Stimulation and Molecular Mechanisms for Browning in Pig Adipocytes","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Elucidating Exogenous Stimulation and Molecular Mechanisms for Browning in Pig Adipocytes","subitem_title_language":"en"}]},"item_type_id":"3","owner":"12","path":["8"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-04-18"},"publish_date":"2024-04-18","publish_status":"0","recid":"2000177","relation_version_is_last":true,"title":["Elucidating Exogenous Stimulation and Molecular Mechanisms for Browning in Pig Adipocytes"],"weko_creator_id":"12","weko_shared_id":-1},"updated":"2024-04-18T04:53:50.582807+00:00"}