Wang J, Xu S, Gao J, Zhang L, Zhang Z, Yang W, Li Y, LiaoS, Zhou H, Liu P, Liang B. SILAC-based quantitative proteomicanalysis of the livers of spontaneous obese and diabetic rhesusmonkeys. Am J Physiol Endocrinol Metab 315: E294–E306, 2018.First published April 17, 2018; doi:10.1152/ajpendo.00016.2018.—Type 2 diabetes mellitus (T2DM) is a severe metabolic disorder thataffects more than 10% of the population worldwide. Obesity is amajor cause of insulin resistance and contributes to the developmentof T2DM. Liver is an essential metabolic organ that plays crucial rolesin the pathogenesis of obesity and diabetes. However, the underlyingmechanisms of liver in the transition of obesity to diabetes are notfully understood. The nonhuman primate rhesus monkey is an appro-priate animal for research of human diseases. Here, we first screenedand selected three individuals of spontaneously diabetic rhesus mon-keys. Interestingly, the diabetic monkeys were obese with a high bodymass index at the beginning, but gradually lost their body weightduring one year of observation. Furthermore, we performed stableisotope labeling with amino acids in cell culture-based quantitativeproteomics to identify proteins and signaling pathways with alteredexpression in the liver of obese and diabetic monkeys. In total, 3,509proteins were identified and quantified, of which 185 proteins dis-played an altered expression level. Gene ontology analysis revealedthat the expression of proteins involved in fatty acids ?-oxidation andgalactose metabolism was increased in obese monkeys; while proteinsinvolved in oxidative phosphorylation and branched chain amino acid(BCAA) degradation were upregulated in diabetic monkeys. In addi-tion, we observed mild apoptosis in the liver of diabetic monkeys,suggesting liver injury at the late onset of diabetes. Taken together,our liver proteomics may reveal a distinct metabolic transition fromfatty acids ?-oxidation in obese monkey to BCAA degradation indiabetic monkeys.