{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:38:37Z","timestamp":1767771517110,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Biomedical Imaging and Bioengineering (NIBIB)","award":["5R21EB02088302"],"award-info":[{"award-number":["5R21EB02088302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: This study evaluated metabolites and lipid composition in the calf muscles of Type 2 diabetes mellitus (T2DM) patients and age-matched healthy controls using multi-dimensional MR spectroscopic imaging. We also explored the association between muscle metabolites, lipids, and intra-abdominal fat in T2DM. Methods: Participants included 12 T2DM patients (60.3 \u00b1 8.6 years), 9 age-matched healthy controls (AMHC) (60.9 \u00b1 7.8 years), and 10 young healthy controls (YHC) (28.3 \u00b1 1.8 years). We acquired the 2D MR spectra of calf muscles using an enhanced accelerated 5D echo-planar correlated spectroscopic imaging (EP-COSI) technique and abdominal MRI with breath-hold 6-point Dixon sequence. Results: In YHC, choline levels were lower in the gastrocnemius (GAS) and soleus (SOL) muscles but higher in the tibialis anterior (TA) compared to AMHC. YHC also showed a higher unsaturation index (U.I.) of extramyocellular lipids (EMCL) in TA, intramyocellular lipids (IMCL) in GAS, carnosine in SOL, and taurine and creatine in TA. T2DM patients exhibited higher choline in TA and myo-inositol in SOL than AMHC, while triglyceride fat (TGFR2) levels in TA were lower. Correlation analyses indicated associations between IMCL U.I. and various metabolites in muscles with liver, pancreas, and abdominal fat estimates in T2DM. Conclusions: This study highlights distinct muscle metabolite and lipid composition patterns across YHC, AMHC, and T2DM subjects. Associations between IMCL U.I. and abdominal fat depots underscore the interplay between muscle metabolism and adiposity in T2DM. These findings provide new insights into metabolic changes in T2DM and emphasize the utility of advanced MR spectroscopic imaging in characterizing muscle-lipid interactions.<\/jats:p>","DOI":"10.3390\/metabo15010025","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:49:13Z","timestamp":1736232553000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lipid Deposition in Skeletal Muscle Tissues and Its Correlation with Intra-Abdominal Fat: A Pilot Investigation in Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"15","author":[{"given":"Manoj Kumar","family":"Sarma","sequence":"first","affiliation":[{"name":"Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Saucedo","sequence":"additional","affiliation":[{"name":"Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5938-1694","authenticated-orcid":false,"given":"Suresh Anand","family":"Sadananthan","sequence":"additional","affiliation":[{"name":"Institute for Human Development and Potential, Agency for Science, Technology, and Research (A*STAR), Singapore 117609, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine Hema","family":"Darwin","sequence":"additional","affiliation":[{"name":"Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ely Richard","family":"Felker","sequence":"additional","affiliation":[{"name":"Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Raman","sequence":"additional","affiliation":[{"name":"Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4096-0722","authenticated-orcid":false,"given":"S. Sendhil","family":"Velan","sequence":"additional","affiliation":[{"name":"Institute for Human Development and Potential, Agency for Science, Technology, and Research (A*STAR), Singapore 117609, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-2585","authenticated-orcid":false,"given":"Michael Albert","family":"Thomas","sequence":"additional","affiliation":[{"name":"Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(16)00618-8","article-title":"Worldwide trends in diabetes since 1980: Pooled analysis of 751 population-based measurement studies with over 4.4 million participants","volume":"387","author":"McLachlan","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diab.37.12.1595","article-title":"Role of insulin resistance in human disease","volume":"37","author":"Reaven","year":"1988","journal-title":"Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kim, M.K. (2014). Clinical characteristics of OGTT-derived hepatic-and muscle insulin resistance in healthy young men. J. Exerc. Nutr. Biochem., 18.","DOI":"10.5717\/jenb.2014.18.4.385"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/j.clinbiochem.2009.05.018","article-title":"Hepatic insulin resistance, metabolic syndrome and cardiovascular disease","volume":"42","author":"Meshkani","year":"2009","journal-title":"Clin. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.amjmed.2006.01.009","article-title":"Etiology of insulin resistance","volume":"119","author":"Petersen","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1007\/s11892-010-0122-6","article-title":"The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes","volume":"10","author":"Cusi","year":"2010","journal-title":"Curr. Diab. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.acra.2014.01.009","article-title":"Abdominal adipose tissue distribution on MRI and diabetes","volume":"21","author":"Mantatzis","year":"2014","journal-title":"Acad. Radiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1017\/S1368980007000614","article-title":"Adipogenesis and lipotoxicity: Role of peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) and PPAR\u03b3coactivator-1 (PGC1)","volume":"10","author":"Gray","year":"2007","journal-title":"Public Health Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E1663","DOI":"10.1152\/ajpendo.00590.2006","article-title":"Increased intrahepatic triglyceride is associated with peripheral insulin resistance: In vivo MR imaging and spectroscopy studies","volume":"293","author":"Hwang","year":"2007","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.dld.2010.01.013","article-title":"Insulin resistance, adipose depots and gut: Interactions and pathological implications","volume":"42","author":"Gastaldelli","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_11","first-page":"785","article-title":"Role of skeletal muscle in insulin resistance and glucose uptake","volume":"10","author":"Merz","year":"2011","journal-title":"Compr. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1749-6632.2002.tb04275.x","article-title":"Desaturation and elongation of fatty acids and insulin action","volume":"967","author":"Vessby","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1749-6632.2000.tb06417.x","article-title":"Observation of Intramyocellular Lipids by1H-Magnetic Resonance Spectroscopy","volume":"904","author":"Boesch","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1194\/jlr.M091942","article-title":"Accumulation of saturated intramyocellular lipid is associated with insulin resistance","volume":"60","author":"Savage","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2147\/OAJSM.S139801","article-title":"Intramyocellular lipids of muscle type in athletes of different sport disciplines","volume":"8","author":"Nakagawa","year":"2017","journal-title":"Open Access J. Sports Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E31","DOI":"10.1152\/ajpendo.1996.271.1.E31","article-title":"Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans","volume":"271","author":"Casey","year":"1996","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/cs0840565","article-title":"Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man","volume":"84","author":"Greenhaff","year":"1993","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cai, C.X., Carlos, S., Solaimani, P., Trivedi, B.J., Tran, C., and Castelino-Prabhu, S. (2019). Nutritional and dietary interventions for nonalcoholic fatty liver disease. Dietary Interventions in Liver Disease, Elsevier.","DOI":"10.1016\/B978-0-12-814466-4.00029-X"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/ajcn\/80.1.163","article-title":"Elevated serum creatine phosphokinase in choline-deficient humans: Mechanistic studies in C2C12 mouse myoblasts","volume":"80","author":"Badea","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.yclnex.2018.12.005","article-title":"Choline administration attenuates aspects of the dystrophic pathology in mdx mice","volume":"24","author":"Alves","year":"2019","journal-title":"Clin. Nutr. Exp."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhao, D., Frohman, M.A., and Blusztajn, J.K. (2001). Generation of choline for acetylcholine synthesis by phospholipase D isoforms. BMC Neurosci., 2.","DOI":"10.1186\/1471-2202-2-16"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Merckx, C., and De Paepe, B. (2022). The role of taurine in skeletal muscle functioning and its potential as a supportive treatment for duchenne muscular dystrophy. Metabolites, 12.","DOI":"10.3390\/metabo12020193"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"eabn9257","DOI":"10.1126\/science.abn9257","article-title":"Taurine deficiency as a driver of aging","volume":"380","author":"Singh","year":"2023","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1968450","DOI":"10.1155\/2018\/1968450","article-title":"Inositols in insulin signaling and glucose metabolism","volume":"2018","author":"Bevilacqua","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(86)80285-X","article-title":"Role of inositol 1, 4, 5-trisphosphate in excitation-contraction coupling in skeletal muscle","volume":"197","author":"Volpe","year":"1986","journal-title":"FEBS Lett."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kr\u0161\u0161\u00e1k, M., Lindeboom, L., Schrauwen-Hinderling, V., Szczepaniak, L.S., Derave, W., Lundbom, J., Befroy, D., Schick, F., Machann, J., and Kreis, R. (2021). Proton magnetic resonance spectroscopy in skeletal muscle: Experts\u2019 consensus recommendations. NMR Biomed., 34.","DOI":"10.1002\/nbm.4266"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/jmri.20786","article-title":"Investigation of muscle lipid metabolism by localized one-and two-dimensional MRS techniques using a clinical 3T MRI\/MRS scanner","volume":"25","author":"Velan","year":"2007","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"R1060","DOI":"10.1152\/ajpregu.90367.2008","article-title":"Distinct patterns of fat metabolism in skeletal muscle of normal-weight, overweight, and obese humans","volume":"295","author":"Velan","year":"2008","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/mrm.1160","article-title":"Localized two-dimensional shift correlated MR spectroscopy of human brain","volume":"46","author":"Thomas","year":"2001","journal-title":"Magn. Reson. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1148\/radiol.10092284","article-title":"Follow-up whole-body assessment of adipose tissue compartments during a lifestyle intervention in a large cohort at increased risk for type 2 diabetes","volume":"257","author":"Machann","year":"2010","journal-title":"Radiology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nagarajan, R., Carpenter, C.L., Lee, C.C., Michael, N., Sarma, M.K., Souza, R., Xu, E., Velan, S.S., Hahn, T.J., and Go, V.-L. (2017). Assessment of lipid and metabolite changes in obese calf muscle using multi-echo echo-planar correlated spectroscopic imaging. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-17529-1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1365-2362.2010.02372.x","article-title":"Liver fat in obesity: Role of type 2 diabetes mellitus and adipose tissue distribution","volume":"41","author":"Bozzetto","year":"2011","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"807","DOI":"10.3945\/ajcn.2008.26955","article-title":"Adipose tissue distribution is different in type 2 diabetes","volume":"89","author":"Gallagher","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"463","DOI":"10.5114\/aoms.2015.52350","article-title":"State of the art paper Central obesity, type 2 diabetes and insulin: Exploring a pathway full of thorns","volume":"11","author":"Papaetis","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMra011775","article-title":"Nonalcoholic fatty liver disease","volume":"346","author":"Angulo","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.3748\/wjg.15.1869","article-title":"Clinical implications of fatty pancreas: Correlations between fatty pancreas and metabolic syndrome","volume":"15","author":"Lee","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ou, H.-Y., Wang, C.-Y., Yang, Y.-C., Chen, M.-F., and Chang, C.-J. (2013). The association between nonalcoholic fatty pancreas disease and diabetes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062561"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/mrm.25988","article-title":"Correlated spectroscopic imaging of calf muscle in three spatial dimensions using group sparse reconstruction of undersampled single and multichannel data","volume":"74","author":"Wilson","year":"2015","journal-title":"Magn. Reson. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mri.2020.07.001","article-title":"Noninvasive assessment of abdominal adipose tissues and quantification of hepatic and pancreatic fat fractions in type 2 diabetes mellitus","volume":"72","author":"Sarma","year":"2020","journal-title":"Magn. Reson. Imaging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/mrm.21604","article-title":"Resolution of creatine and phosphocreatine 1H signals in isolated human skeletal muscle using HR-MAS 1H NMR","volume":"59","author":"Chen","year":"2008","journal-title":"Magn. Reson. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"MRI.S10489","DOI":"10.4137\/MRI.S10489","article-title":"Characterization of intra-myocellular lipids using 2D localized correlated spectroscopy and abdominal fat using MRI in type 2 diabetes","volume":"5","author":"Srikanthan","year":"2012","journal-title":"Magn. Reson. Insights"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21630","DOI":"10.1002\/jcp.28821","article-title":"Impact of different ectopic fat depots on cardiovascular and metabolic diseases","volume":"234","author":"Ferrara","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Correa-de-Araujo, R., Addison, O., Miljkovic, I., Goodpaster, B.H., Bergman, B.C., Clark, R.V., Elena, J.W., Esser, K.A., Ferrucci, L., and Harris-Love, M.O. (2020). Myosteatosis in the context of skeletal muscle function deficit: An interdisciplinary workshop at the National Institute on Aging. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00963"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/mrm.24168","article-title":"Skeletal muscle 1H MRSI before and after prolonged exercise. I. muscle specific depletion of intramyocellular lipids","volume":"68","author":"Vermathen","year":"2012","journal-title":"Magn. Reson. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E1099","DOI":"10.1210\/jc.2011-3243","article-title":"Intramyocellular lipid is associated with visceral adiposity, markers of insulin resistance, and cardiovascular risk in prepubertal children: The EPOCH study","volume":"97","author":"Brumbaugh","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:24:20Z","timestamp":1759919060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["metabo15010025"],"URL":"https:\/\/doi.org\/10.3390\/metabo15010025","relation":{},"ISSN":["2218-1989"],"issn-type":[{"type":"electronic","value":"2218-1989"}],"subject":[],"published":{"date-parts":[[2025,1,7]]}}}