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Duan"],"technology_type":["Mass Spectrometry","Bottom-up proteomics","Data-independent acquisition"],"software":["Not available"],"submitter_keywords":["Obesity","Calorie restriction","Insulin resistance"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD067874"],"tissue":["Skeletal Muscle","Liver","Epididymal White Adipose Tissue","Subcutaneous Adipose Tissue"],"sample_protocol":["Detailed sample processing protocols are provided in the associated manuscript."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Detailed data processing protocols are provided in the associated manuscript."],"omics_type":["Proteomics"],"labhead":["David Savage"],"instrument_platform":[""],"labhead_affiliation":["Institute of Metabolic Science, University of Cambridge"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"publication":["42090498 Duan X, Davis LM, Patel S, Bidault G, Long L, Jenkins B, Yi Y, Pushpa P, Wesseling JR, Koulman A, Vidal-Puig A, Fazakerley DJ, Savage DB. Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction. Sci Adv. 2026 12(19):eaed0535 10.1126/sciadv.aed0535"],"submitter_mail":["xd253@cam.ac.uk"],"submitter_affiliation":["Institute of Metabolic Science"],"submitter_country":["United Kingdom"],"pubmed_abstract":["Insulin resistance (IR) links obesity to metabolic disorders. While weight loss reverses IR, we show that calorie reduction (CR) can do so in obese mice within a day before significant weight loss. In contrast to whole-body IR, individual tissues do not revert to their original chow diet-fed states after CR. In the liver, improved insulin sensitivity correlates with reduced triacylglycerol and diacylglycerol and protein kinase C epsilon activity, alongside substantially decreased de novo lipogenesis and increased ketones. In muscle, insulin-sensitive glucose disposal was restored, whereas obesity-associated adipose tissue changes largely persisted following CR, specifically the reduction in fasting lipolytic activity mediated at least, in part, by lower β-adrenergic receptor 3 expression. This, combined with enhanced oxidative pathways in muscle and liver, resulted in lowered plasma free fatty acid levels and muscle and liver lipids, facilitating insulin-stimulated glucose disposal and thus restored insulin sensitivity."],"pubmed_title":["Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction."],"pubmed_authors":["Duan Xiaowen X, Davis Lucy M LM, Patel Satish S, Bidault Guillaume G, Long Lu L, Jenkins Benjamin B, Yi Yao Y, Pushpa Pushpa P, Wesseling Julia R JR, Koulman Albert A, Vidal-Puig Antonio A, Fazakerley Daniel J DJ, Savage David B DB"],"additional_accession":[]},"is_claimable":false,"name":"Understanding how reduced energy intake rapidly alleviates obesity associated insulin resistance","description":"Insulin resistance (IR) underpins the relationship between obesity and its associated metabolic disorders. Negative energy balance alleviates IR rapidly, though the mechanism remains unclear. Here, we show that in obese mice, IR can be reversed by calorie reduction (CR) within a day. In the liver, improved insulin sensitivity correlates with reduced tri-(TAG) and diacylglycerol (DAG) concentrations and decreased protein kinase C epsilon (PKCε) activation. In muscle, insulin-stimulated glucose disposal was also restored, whereas obesity-related changes in adipose tissue largely persisted following CR. Specifically, obesity is associated with reduced fasting lipolytic activity in adipose tissue, likely mediated in part by lower beta-adrenergic receptor 3 (ADRB3) expression. Acute CR did not reverse these adipose changes but further reduced plasma free fatty acid (FA) levels by dampening lipolytic activity and upregulating oxidative pathways in muscle and liver. This facilitates insulin-stimulated glucose disposal and restores insulin sensitivity.","dates":{"publication":"2026-06-08","submission":"2025-08-29"},"accession":"PXD067874","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NEWT:32046","NEWT:544496","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:1129","NEWT:309807","NEWT:10245","NEWT:55153","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:43186","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:35786","NEWT:1580","NEWT:96731","NEWT:383379","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:7959","NEWT:2261","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:192875","NEWT:1214915","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:5757","NCBITaxon:4563","NEWT:5755","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:145458","NEWT:633149","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1235816","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:2065263","NEWT:1772","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:3702","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:9483","NEWT:333760","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:1502","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:1313","NEWT:1218097","NCBITaxon:50557","NEWT:39251","NEWT:39491","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NEWT:272634","NEWT:9031","NEWT:1872122","NEWT:1308","NEWT:7091","NEWT:1034015","NEWT:760568","NEWT:141262","NEWT:108931","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:97477","NEWT:7111","NEWT:347515","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:4090","NEWT:4092","NEWT:9541","NEWT:8694","NEWT:4093","NEWT:4096","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:941442","NEWT:536088","NEWT:13076","NEWT:1226408","NEWT:7108","NEWT:40479","NEWT:43989","NEWT:4076","NEWT:142615","NEWT:317","NEWT:1006581","NEWT:885318","NEWT:39488","NEWT:550","NEWT:4081","NEWT:273068","NEWT:554","NEWT:98334","NEWT:451516","NEWT:4084","NEWT:63577","NEWT:36185","NEWT:1225786","NEWT:7574","NEWT:1715256","NEWT:30640","NEWT:575412","NEWT:929793","NEWT:29204","NEWT:28112","NEWT:114155","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:6239","NEWT:162425","NEWT:216257","NEWT:102169","NEWT:9986","NEWT:4054","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8655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