{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T21:52:53Z","timestamp":1794433973670,"version":"4.9.1"},"reference-count":113,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,27]],"date-time":"2019-07-27T00:00:00Z","timestamp":1564185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K17953"],"award-info":[{"award-number":["18K17953"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K13231"],"award-info":[{"award-number":["17K13231"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H02179"],"award-info":[{"award-number":["17H02179"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity causes various health problems, such as type 2 diabetes, non-alcoholic fatty liver disease, and cardio- and cerebrovascular diseases. Metabolic organs, particularly white adipose tissue (WAT) and liver, are deeply involved in obesity. WAT contains many adipocytes with energy storage capacity and secretes adipokines depending on the obesity state, while liver plays pivotal roles in glucose and lipid metabolism. This review outlines and underscores the relationship between obesity and lysosomal functions, including lysosome biogenesis, maturation and activity of lysosomal proteases in WAT and liver. It has been revealed that obesity-induced abnormalities of lysosomal proteases contribute to inflammation and cellular senescence in adipocytes. Previous reports have demonstrated obesity-induced ectopic lipid accumulation in liver is associated with abnormality of lysosomal proteases as well as other lysosomal enzymes. These studies demonstrate that lysosomal dysfunction in WAT and liver underlies part of the obesity-related pathology, raising the possibility that strategies to modulate lysosomal function may be effective in preventing or treating the metabolic syndrome.<\/jats:p>","DOI":"10.3390\/ijms20153688","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T03:06:58Z","timestamp":1564369618000},"page":"3688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6716-1544","authenticated-orcid":false,"given":"Yuhei","family":"Mizunoe","sequence":"first","affiliation":[{"name":"Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-0322","authenticated-orcid":false,"given":"Masaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoma","family":"Tagawa","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8710-5232","authenticated-orcid":false,"given":"Yoshimi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"},{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-5572","authenticated-orcid":false,"given":"Hitoshi","family":"Shimano","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"},{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan"},{"name":"Life Science Center, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan"},{"name":"Japan Agency for Medical Research and Development\u2013Core Research for Evolutional Science and Technology (AMED-CREST), Chiyoda-ku, Tokyo 100-1004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-0777","authenticated-orcid":false,"given":"Yoshikazu","family":"Higami","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nature05487","article-title":"Mechanisms linking obesity with cardiovascular disease","volume":"444","author":"Mertens","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1210\/er.2017-00111","article-title":"Obesity Pathogenesis: An Endocrine Society Scientific Statement","volume":"38","author":"Schwartz","year":"2017","journal-title":"Endocr. 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