Insulin and diet-induced changes in the ubiquitin-modified proteome of rat liver.
Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions. KEGG pathway analysis of these proteins identified enrichment of metabolic pathways, TCA cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and carbon metabolism, with similar pathways altered by diet and insulin resistance. Thus, the rat liver ubiquitome is sensitive to diet and insulin stimulation and this is perturbed in insulin resistance.
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Shilpa R
SR
Nagarajan
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Amanda E
AE
Brandon
Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Jessie A
JA
McKenna
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Harrison C
HC
Shtein
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Thinh Q
TQ
Nguyen
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Eurwin
E
Suryana
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Philip
P
Poronnik
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Gregory J
GJ
Cooney
Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Darren N
DN
Saunders
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
Andrew J
http://orcid.org/0000-0003-3922-1137
AJ
Hoy
D000818:Animals; D002244:Carbon / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D004032:Diet / Q000379:methods; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D020543:Proteome / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage*; D025801:Ubiquitin / Q000378:metabolism*
D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; D020543:Proteome; D025801:Ubiquitin; D013395:Sucrose; D002244:Carbon