{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:41:01Z","timestamp":1765280461332,"version":"3.41.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-05949-3","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T16:23:48Z","timestamp":1751387028000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Low leg fat mass is associated with low insulin sensitivity, inflammatory markers, and \u03b2-cell dysfunction in non-obese Japanese people"],"prefix":"10.1038","volume":"15","author":[{"given":"Satomi","family":"Minato-Inokawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Tsuboi-Kaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mika","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Kitaoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Kurata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Kazumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Fukuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"5949_CR1","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.cmet.2017.07.008","volume":"26","author":"N Stefan","year":"2017","unstructured":"Stefan, N., Schick, F. & H\u00e4ring, H. U. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 26, 292\u2013300 (2017).","journal-title":"Cell Metab."},{"key":"5949_CR2","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/S2213-8587(20)30110-8","volume":"8","author":"N Stefan","year":"2020","unstructured":"Stefan, N. Causes, consequences, and treatment of metabolically unhealthy fat distribution. Lancet Diabetes Endocrinol. 8, 616\u2013627 (2020).","journal-title":"Lancet Diabetes Endocrinol."},{"key":"5949_CR3","first-page":"293","volume":"27","author":"M Takeuchi","year":"2018","unstructured":"Takeuchi, M., Tsuboi, A., Kurata, M., Kazumi, T. & Fukuo, K. Associations of postprandial lipemia with trunk\/leg fat ratio in young normal weight women independently of fat mass and insulin resistance. Asia Pac. J. Clin. Nutr. 27, 293\u2013299 (2018).","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"5949_CR4","doi-asserted-by":"publisher","first-page":"117371","DOI":"10.1016\/j.atherosclerosis.2023.117371","volume":"386","author":"E Gagnon","year":"2023","unstructured":"Gagnon, E., Paulin, A., Mitchell, P. L. & Arsenault, B. J. Disentangling the impact of gluteofemoral versus visceral fat accumulation on cardiometabolic health using sex-stratified Mendelian randomization. Atherosclerosis 386, 117371 (2023).","journal-title":"Atherosclerosis"},{"key":"5949_CR5","doi-asserted-by":"publisher","first-page":"S253","DOI":"10.1301\/nr.2007.dec.S253-S259","volume":"65","author":"PM Ridker","year":"2007","unstructured":"Ridker, P. M. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr. Rev. 65, S253\u2013S259 (2007).","journal-title":"Nutr. Rev."},{"key":"5949_CR6","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.diabres.2014.04.006","volume":"105","author":"N Esser","year":"2014","unstructured":"Esser, N., Legrand-Poels, S., Piette, J., Scheen, A. J. & Paquot, N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res. Clin. Pract. 105, 141\u2013150 (2014).","journal-title":"Diabetes Res. Clin. Pract."},{"key":"5949_CR7","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.2741\/3812","volume":"16","author":"C Espinola-Klein","year":"2011","unstructured":"Espinola-Klein, C., Gori, T., Blankenberg, S. & Munzel, T. Inflammatory markers and cardiovascular risk in the metabolic syndrome. Front. Biosci. (Landmark Ed.) 16, 1663\u20131674 (2011).","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"5949_CR8","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1152\/physrev.00033.2011","volume":"93","author":"A Tchernof","year":"2013","unstructured":"Tchernof, A. & Despr\u00e9s, J. P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359\u2013404 (2013).","journal-title":"Physiol. Rev."},{"key":"5949_CR9","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1038\/s41366-021-00898-z","volume":"45","author":"C Bridger Staatz","year":"2021","unstructured":"Bridger Staatz, C. et al. Life course socioeconomic position and body composition in adulthood: a systematic review and narrative synthesis. Int. J. Obes. (London) 45, 2300\u20132315 (2021).","journal-title":"Int. J. Obes. (London)"},{"key":"5949_CR10","doi-asserted-by":"publisher","first-page":"633","DOI":"10.5551\/jat.11940","volume":"19","author":"M Tanaka","year":"2012","unstructured":"Tanaka, M., Yoshida, T., Bin, W., Fukuo, K. & Kazumi, T. FTO, abdominal adiposity, fasting hyperglycemia associated with elevated HbA1c in Japanese middle-aged women. J. Atheroscler. Thromb. 19, 633\u2013642 (2012).","journal-title":"J. Atheroscler. Thromb."},{"key":"5949_CR11","doi-asserted-by":"publisher","first-page":"19234","DOI":"10.1038\/s41598-024-70396-5","volume":"14","author":"S Minato-Inokawa","year":"2024","unstructured":"Minato-Inokawa, S. et al. The different associations of serum gamma-glutamyl transferase and alanine aminotransferase with insulin secretion, \u03b2-cell function, and insulin resistance in non-obese Japanese. Sci. Rep. 14, 19234 (2024).","journal-title":"Sci. Rep."},{"key":"5949_CR12","doi-asserted-by":"publisher","first-page":"1289485","DOI":"10.1155\/2018\/1289485","volume":"2018","author":"B Wu","year":"2018","unstructured":"Wu, B. et al. Different associations of trunk and lower-body fat mass distribution with cardiometabolic risk factors between healthy middle-aged men and women. Int. J. Endocrinol. 2018, 1289485 (2018).","journal-title":"Int. J. Endocrinol."},{"key":"5949_CR13","first-page":"215","volume":"3","author":"M Takeuchi","year":"2022","unstructured":"Takeuchi, M. et al. Weight trajectory since birth, current body composition, dietary intake, and glucose tolerance in young underweight Japanese women. Womens Health Rep. (New Rochelle) 3, 215\u2013221 (2022).","journal-title":"Womens Health Rep. (New Rochelle)"},{"key":"5949_CR14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12933-018-0733-9","volume":"17","author":"X Bao","year":"2018","unstructured":"Bao, X. et al. Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the \u2018common soil\u2019 hypothesis. Cardiovasc. Diabetol. 17, 87 (2018).","journal-title":"Cardiovasc. Diabetol."},{"key":"5949_CR15","unstructured":"American Diabetes Association Professional Practice Committee; 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes\u20142025. Diabetes Care. 48(Supplement 1), S27\u201349 (2025)."},{"key":"5949_CR16","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","volume":"120","author":"KG Alberti","year":"2009","unstructured":"Alberti, K. G. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 120, 1640\u20135 (2009).","journal-title":"Circulation."},{"key":"5949_CR17","doi-asserted-by":"publisher","first-page":"101280","DOI":"10.1016\/j.aohep.2023.101280","volume":"29","author":"J Lee","year":"2024","unstructured":"Lee, J. et al. Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT. Ann. Hepatol. 29, 101280 (2024).","journal-title":"Ann. Hepatol."},{"key":"5949_CR18","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/BF00280883","volume":"28","author":"DR Matthews","year":"1985","unstructured":"Matthews, D. R. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412\u2013419 (1985).","journal-title":"Diabetologia"},{"key":"5949_CR19","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1210\/jc.2017-00047","volume":"102","author":"E S\u00f8ndergaard","year":"2017","unstructured":"S\u00f8ndergaard, E., Espinosa De Ycaza, A. E., Morgan-Bathke, M. & Jensen, M. D. How to measure adipose tissue insulin sensitivity. J. Clin. Endocrinol. Metab. 102, 1193\u20139 (2017).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"5949_CR20","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","volume":"22","author":"M Matsuda","year":"1999","unstructured":"Matsuda, M. & DeFronzo, R. A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462\u20131470 (1999).","journal-title":"Diabetes Care"},{"key":"5949_CR21","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2337\/diacare.23.3.295","volume":"23","author":"M Stumvoll","year":"2000","unstructured":"Stumvoll, M. et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23, 295\u2013301 (2000).","journal-title":"Diabetes Care"},{"key":"5949_CR22","doi-asserted-by":"publisher","first-page":"335","DOI":"10.2337\/dc08-1478","volume":"32","author":"KM Utzschneider","year":"2009","unstructured":"Utzschneider, K. M. et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care 32, 335\u2013341 (2009).","journal-title":"Diabetes Care"},{"key":"5949_CR23","doi-asserted-by":"publisher","first-page":"e7038","DOI":"10.1371\/journal.pone.0007038","volume":"4","author":"TL Kelly","year":"2009","unstructured":"Kelly, T. L., Wilson, K. E. & Heymsfield, S. B. Dual energy X-Ray absorptiometry body composition reference values from NHANES. PLoS ONE 4, e7038 (2009).","journal-title":"PLoS ONE"},{"key":"5949_CR24","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1002\/oby.20028","volume":"21","author":"X Zhang","year":"2013","unstructured":"Zhang, X., Hu, E. A., Wu, H., Malik, V. & Sun, Q. Associations of leg fat accumulation with adiposity-related biological factors and risk of metabolic syndrome. Obesity (Silver Spring) 21, 824\u2013830 (2013).","journal-title":"Obesity (Silver Spring)"},{"key":"5949_CR25","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12933-017-0536-4","volume":"16","author":"E Han","year":"2017","unstructured":"Han, E. et al. Anatomic fat depots and cardiovascular risk: a focus on the leg fat using nationwide surveys (KNHANES 2008\u20132011). Cardiovasc. Diabetol. 16, 54 (2017).","journal-title":"Cardiovasc. Diabetol."},{"key":"5949_CR26","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.3803\/EnM.2021.1087","volume":"36","author":"HM Kim","year":"2021","unstructured":"Kim, H. M. & Lee, Y. H. The leg fat to total fat ratio is associated with lower risks of non-alcoholic fatty liver disease and less severe hepatic fibrosis: Results from Nationwide Surveys (KNHANES 2008\u20132011). Endocrinol. Metab. (Seoul) 36, 1232\u20131242 (2021).","journal-title":"Endocrinol. Metab. (Seoul)"},{"key":"5949_CR27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40885-021-00190-2","volume":"28","author":"A Visaria","year":"2022","unstructured":"Visaria, A., Lo, D., Maniar, P., Dave, B. & Joshi, P. Leg and arm adiposity is inversely associated with diastolic hypertension in young and middle-aged United States adults. Clin. Hypertens. 28, 3 (2022).","journal-title":"Clin. Hypertens."},{"key":"5949_CR28","doi-asserted-by":"publisher","first-page":"372","DOI":"10.2337\/diacare.27.2.372","volume":"27","author":"MB Snijder","year":"2004","unstructured":"Snijder, M. B. et al. Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels: the Hoorn study. Diabetes Care 27, 372\u2013377 (2004).","journal-title":"Diabetes Care"},{"key":"5949_CR29","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.2337\/dc11-0616","volume":"34","author":"LA Kosmiski","year":"2011","unstructured":"Kosmiski, L. A. et al. Study of fat redistribution and metabolic change in HIV Infection (FRAM). Association of increased upper trunk and decreased leg fat with 2-h glucose in control and HIV-infected persons. Diabetes Care 34, 2448\u201353 (2011).","journal-title":"Diabetes Care"},{"key":"5949_CR30","doi-asserted-by":"publisher","first-page":"365","DOI":"10.5551\/jat.7229","volume":"18","author":"S Tanaka","year":"2011","unstructured":"Tanaka, S. et al. Associations of lower-body fat mass with favorable profile of lipoproteins and adipokines in healthy, slim women in early adulthood. J. Atheroscler. Thromb. 18, 365\u2013372 (2011).","journal-title":"J. Atheroscler. Thromb."},{"key":"5949_CR31","doi-asserted-by":"publisher","first-page":"18590","DOI":"10.1038\/s41598-024-69181-1","volume":"14","author":"S Minato-Inokawa","year":"2024","unstructured":"Minato-Inokawa, S. et al. Associations of adipose insulin resistance index with pancreatic \u03b2 cell function (inverse) and glucose excursion (positive) in young Japanese women. Sci. Rep. 14, 18590 (2024).","journal-title":"Sci. Rep."},{"key":"5949_CR32","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1210\/js.2018-00372","volume":"3","author":"R Ye","year":"2019","unstructured":"Ye, R., Onodera, T. & Scherer, P. E. Lipotoxicity and \u03b2 cell maintenance in obesity and type 2 diabetes. J. Endocr. Soc. 3, 617\u2013631 (2019).","journal-title":"J. Endocr. Soc."},{"key":"5949_CR33","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-024-06309-y","author":"G Yu","year":"2024","unstructured":"Yu, G. et al. Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes. Diabetologia https:\/\/doi.org\/10.1007\/s00125-024-06309-y (2024).","journal-title":"Diabetologia"},{"key":"5949_CR34","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/s41591-024-02865-3","volume":"30","author":"K Smith","year":"2024","unstructured":"Smith, K. et al. Multi-ancestry polygenic mechanisms of type 2 diabetes. Nat. Med. 30, 1065\u20131074 (2024).","journal-title":"Nat. Med."},{"key":"5949_CR35","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/ijo.2010.137","volume":"35","author":"NJ Timpson","year":"2011","unstructured":"Timpson, N. J. et al. C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization. Int. J. Obes. (London). 35, 300\u2013308 (2011).","journal-title":"Int. J. Obes. (London)."},{"key":"5949_CR36","doi-asserted-by":"publisher","first-page":"e1001765","DOI":"10.1371\/journal.pmed.1001765","volume":"11","author":"P W\u00fcrtz","year":"2014","unstructured":"W\u00fcrtz, P. et al. Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change. PLoS Med. 11, e1001765 (2014).","journal-title":"PLoS Med."},{"key":"5949_CR37","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1093\/ajcn\/nqaa056","volume":"111","author":"S Palaniswamy","year":"2020","unstructured":"Palaniswamy, S. et al. Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study. Am. J. Clin. Nutr. 111, 1036\u20131047 (2020).","journal-title":"Am. J. Clin. Nutr."},{"key":"5949_CR38","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.2337\/dc09-0176","volume":"32","author":"E Lapice","year":"2009","unstructured":"Lapice, E. et al. Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people. Diabetes Care 32, 1734\u20131736 (2009).","journal-title":"Diabetes Care"},{"key":"5949_CR39","doi-asserted-by":"publisher","first-page":"932","DOI":"10.2337\/dc08-1856","volume":"32","author":"S Sam","year":"2009","unstructured":"Sam, S. et al. Relation of abdominal fat depots to systemic markers of inflammation in type 2 diabetes. Diabetes Care 32, 932\u2013937 (2009).","journal-title":"Diabetes Care"},{"key":"5949_CR40","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/ajh.2012.92","volume":"25","author":"M Lee","year":"2012","unstructured":"Lee, M. et al. Associations between trunk, leg and total body adiposity with arterial stiffness. Am. J. Hypertens. 25, 1131\u20131137 (2012).","journal-title":"Am. J. Hypertens."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-05949-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-05949-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-05949-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T16:23:52Z","timestamp":1751387032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-05949-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5949"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-05949-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"20 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was approved by the Ethics Committees of the Mukogawa Women\u2019s University (No. 07-28 on 19\/02\/2008).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"21194"}}