JPOST Repositoryapplication/xmlhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_05.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_03.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_07.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_09.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_01.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_05.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_02.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_07.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_04.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_06.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_02.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_08.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_08.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_10.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_03.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_10.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_04.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_liver_1000ng_09.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_01.rawhttps://storage.jpostdb.org/JPST000927/files/20171209_iBAQ_Muscle_600ng_06.rawprimary200OKProteomicsShinya KurodaMus Musculus (mouse)https://repository.jpostdb.org/entry/JPST000927Department of Omics and Systems Biology, Niigata UniversityjPOSTSystemic metabolic homeostasis is regulated by inter-organ metabolic cycles involving multiple organs. Obesity impairs inter-organ metabolic cycles, resulting in metabolic diseases. The systemic landscape of dysregulated inter-organ metabolic cycles in obesity has yet to be explored. Here, we measured the transcriptome, proteome, and metabolome in the liver and skeletal muscle and the metabolome in blood of fasted wild-type and leptin-deficient obese (<i>ob</i>/<i>ob</i>) mice, identifying components with differential abundance and differential regulation in <i>ob</i>/<i>ob</i> mice. By constructing and evaluating the trans-omic network controlling the differences in metabolic reactions between fasted wild-type and <i>ob</i>/<i>ob</i> mice, we provided potential mechanisms of the obesity-associated dysfunctions of metabolic cycles between liver and skeletal muscle involving glucose-alanine, glucose-lactate, and ketone bodies. Our study revealed obesity-associated systemic pathological mechanisms of dysfunction of inter-organ metabolic cycles.Trans-omic analysis reveals obesity-associated dysregulation of inter-organ metabolic cycles between the liver and skeletal muscle.Egami Riku R, Kokaji Toshiya T, Hatano Atsushi A, Yugi Katsuyuki K, Eto Miki M, Morita Keigo K, Ohno Satoshi S, Fujii Masashi M, Hironaka Ken-Ichi KI, Uematsu Saori S, Terakawa Akira A, Bai Yunfan Y, Pan Yifei Y, Tsuchiya Takaho T, Ozaki Haruka H, Inoue Hiroshi H, Uda Shinsuke S, Kubota Hiroyuki H, Suzuki Yutaka Y, Matsumoto Masaki M, Nakayama Keiichi I KI, Hirayama Akiyoshi A, Soga Tomoyoshi T, Kuroda Shinya Sskeletal muscle system., Plantaris, Gastrocnemius Muscle, Anterior, determination, Laboratory, Skeletal, Mus domesticus, Anterior Tibial Muscle, mouse, total expressed protein, Muscle, House Mouse, skeletal muscle, jecur, Soleus, somatic muscle, House, Mus, Voluntary Muscle, Voluntary, chemical analysis, Voluntary Muscles, Mus musculus domesticus, Mice, Mus musculus, Soleus Muscle, Swiss, Tibial Muscle, mice, Swiss Mouse, iecur, House Mice, Swiss Mice, Skeletal Muscles, domesticus, Laboratory Mice, Livers, Skeletal Muscle, Plantaris Muscle, Muscles, Mouse, assay, house mouse, Anterior Tibial, Gastrocnemius, Proteomes, Laboratory Mouse, striated muscleMGC130048, L-Lactic Acid, Plantaris, Ob Gene Product, Anterior, Laboratory, Skeletal, Glukose, Mus domesticus, Anterior Tibial Muscle, 2-Hydroxy-, Gene Expression Profile, A4, Monohydrate, D-Lactic Acid, CASP-14, Profiles, (DL)-Isomer, House Mouse, Adiposis, Social Controls, element, Obese, unspecified, Ketone, Dextrose, Formal Social Controls, Metabolic Profiles, organ, A, gamma sarcoglycan, Thesaurismosis, reference sample, ketone bodies, 2-Hydroxypropionic Acid, Metabolic disease, iecur, Swiss Mice, alanina, L Lactic Acid, Signatures, DL-glucose, Social, glucose, Muscles, Expression Signature, Transcriptomes, gamma-sarcoglycan, METABOLISM DISORDER NOS, associated, MD - Metabolic disorders, Gastrocnemius, Obese Protein, Sarcolactic Acid, obese, Expression Profiles, SG-gamma, CASP14, mouse, Abufène, Gene Expression, positive regulation of homeostatic process, Voluntary Muscle, Voluntary, Expression Signatures, Mini-ICE, Obesity [Ambiguous], Obese (finding), Diseases, Voluntary Muscles, OBESITY, NOS, sarcoglycan, (alpha-D)-Isomer, Expression Profile, D Lactic Acid, Transcriptome Profiles, Mus musculus, D-Glucose, METAB DIS, Caspase-14 subunit p10, mice, 2-Hydroxypropanoic Acid, Swiss Mouse, Control, Adiposity, OBESITY NOS, Caspase-14 subunit p19, b-lactate, Controls, gamma (35kDa dystrophin-associated glycoprotein), MICE, domesticus, DMDA, D Glucose, 35kD dystrophin-associated glycoprotein, Mouse, Unspecified disorder of metabolism, Glucose Monohydrate, Regulation, Proteomes, Regulations, gluco-hexose, 3.4.22.-, Ammonium, Gastrocnemius Muscle, Metabolic Disease, SGCG_HUMAN, Transcriptome Profile, Glucose, Bodies, 2 Hydroxypropionic Acid, obesity disease, L Isomer, Gene, mini-ICE, beta-lactate, skeletal muscle, TYPE, Gene Product, Propanoic Acid, jecur, Obesity, DAGA4, (2S)-, Generalized metabolic disorder, House, 35DAG, metabolism disorder, Mus musculus domesticus, element., MAM, gamma-SG, Metabolic Profile, SCG3, Mice, portion of blood, Generalized metabolic disorder (disorder), study, disease of metabolism, MeCH(OH)CO2 anion, Metabolomes, Tibial Muscle, Swiss, Profile, dysfunction, Having too much body fat, Ammonium Lactate, Overweight and obesity, Skeletal Muscles, Alanine, Skeletal Muscle, Plantaris Muscle, anatomical unit, body organ, negative regulation of homeostatic process, Acetone Bodies, Metabolic disorder, ALA, 2-hydroxypropionate, Anterior Tibial, Anhydrous, Controlled, striated muscle, Acetone, Autoregulation, Disease, Controlling, Lactate, Transcriptome, 2 Hydroxypropanoic Acid, whole blood, (beta-D)-Isomer, 35 kDa dystrophin-associated glycoprotein, Formal Social Control, vertebrate blood, total expressed protein, ion(1-), L Alanine, L-Alanine, Muscle, L-Isomer, disorder of metabolism NOS (disorder), obesity, SGCG, LGMD2C, whole transcriptome, 2-Aminopropionic acid, Soleus, somatic muscle, Mus, Social Control, disorder of metabolism NOS, Gene Expression Signatures, Generalised metabolic disorder, Gene Expression Signature, regulation of homeostatic process, L-Isomer Alanine, obesity disorder, Obesity (disorder), Metabolic disorders, (L)-Alanine, Metabolic disease (disorder), Soleus Muscle, DMDA1, Thesaurismoses, Metabolic, metabolic disease, Obesity NOS, ob, OB, House Mice, 2-Aminopropanoic acid, Alanin, pathophysiology, Anhydrous Dextrose, Laboratory Mice, Livers, Obese Gene Product, Metabolic Diseases, (2R)-, Gene Expression Profiles, 2-hydroxypropanoic acid, SCARMD2, Ob, regulation, Signature, Ob Protein, Laboratory Mouse, skeletal muscle system, Glcskeletal muscle system., Plantaris, Gastrocnemius Muscle, Anterior, determination, Skeletal, Anterior Tibial Muscle, obesity disease, Muscle, skeletal muscle, Adiposis, obesity, element, jecur, Obesity, Soleus, Obese, somatic muscle, unspecified, Voluntary Muscle, Voluntary, chemical analysis, Obesity [Ambiguous], Obese (finding), Voluntary Muscles, OBESITY, obesity disorder, Obesity (disorder), organ, Soleus Muscle, Tibial Muscle, Obesity NOS, Having too much body fat, iecur, Adiposity, OBESITY NOS, Overweight and obesity, Skeletal Muscles, Livers, Skeletal Muscle, Plantaris Muscle, Muscles, anatomical unit, body organ, assay, associated, Anterior Tibial, Gastrocnemius, striated muscleWater, MGC130048, Plantaris, E 920, Anterior, determination, Laboratory, Skeletal, Mus domesticus, Anterior Tibial Muscle, classic hairy cell leukaemia, H(2)O, A4, BOUND WATER, CASP-14, SDH, Hydrogenchlorid, Basodexan, protein, oxidane, mg/ml, House Mouse, CG11121, WATER, HOH, Alkylations, 2-Propanone, SDS, Polypeptides, old, hydrogen chloride, peptido, congenital, B1, Min, 2-amino-3-mercaptopropanoic acid, Cystein, protein aggregate, methyl ketone, DmelCG42273, treatment, gamma sarcoglycan, C, peptides, cisteina, E927b, Tissue, iecur, min, chemical analysis., Swiss Mice, mAPC, achromobacter beta-lytic protease (blp), purification, SO, lipomatosis of pancreas, AI047805, isolation and purification, Wasserstoffchlorid, Muscles, SOLO DANCERS, Propanon, scientific observation, D1, disease management, Therapies, gamma-sarcoglycan, dihydridooxygen, Shwachman-Bodian syndrome, TEAB, Half Cystine, dihydrogen oxide, Gastrocnemius, So, Therapy, Zinc Cysteinate, dimethylketone, SG-gamma, CASP14, mouse, aqua, Dmel_CG7826, AI836084, classic hairy cell leukemia, Cys, ur, Aceton, carbamide, H2O, Pyroacetic ether, Dm1, Voluntary Muscle, Voluntary, Mini-ICE, Voluntary Muscles, Chlorwasserstoff, lysyl endoprotease, sarcoglycan, (2R)-2-amino-3-sulfanylpropanoic acid, Dmel_CG7835, Hydrogen Oxide, Mnb, MNB, Mus musculus, Caspase-14 subunit p10, mice, HCl, Swiss Mouse, Shwachman-Diamond type metaphyseal dysplasia, hydrogen hydroxide, Caspase-14 subunit p19, L-Cysteine, Shwachman syndrome, AW124434, gamma (35kDa dystrophin-associated glycoprotein), MICE, beta-Ketopropane, Treatments, acqua, L-Cystein, domesticus, H2NC(O)NH2, DMDA, 35kD dystrophin-associated glycoprotein, Acetamide, Mouse, Wasser, Polypeptide, chlorane, 1728, 3.4.22.-, F10B6_15, Gastrocnemius Muscle, Cysteine Hydrochloride, SGCG_HUMAN, chlorure d'hydrogene, L-Zystein, Gene, mini-ICE, Carbamide, protein-containing complex, skeletal muscle, TYPE, F10B6.15, CG7826, agua, jecur, DAGA4, Karbamid, propanone, DmelCG11121, House, isolation, Harnstoff, 35DAG, dimethylcetone, CG7835, Gene Products, Mus musculus domesticus, CG42273, Half-Cystine, Carmol, MAM, gamma-SG, SCG3, Mice, cloruro de hidrogeno, somda, Hydrogen chloride, Tibial Muscle, Swiss, L Cysteine, E-920, particle-bound, 4733401P19Rik, blocked, Hcys, eau, Skeletal Muscles, Solution, Skeletal Muscle, Plantaris Muscle, CYSTEINE, Suspension, congenital lipomatosis of pancreas, FREE CYSTEINE, peptidos, Azeton, (2R)-2-amino-3-mercaptopropanoic acid, Dimethyl ketone, Anterior Tibial, 2-iodo-, TCEP, PTHB1, striated muscle, Drl, measuring, DYRK1, Dimethylketon, 35 kDa dystrophin-associated glycoprotein, protein complex, Proteins, chloridohydrogen, Muscle, Peptide, SGCG, Mdu, LGMD2C, Soleus, [HCl], somatic muscle, Temperatures, native protein, Mus, carbonyldiamide, mda, C18, water, chemical analysis, Protein, Hydrochloride, Dyrk1, ami, Zystein, Achromobacter protease I, AU020952, Soleus Muscle, DMDA1, uree, 2-amino-3-sulfanylpropanoic acid, med, CC1, SWDS, L-2-Amino-3-mercaptopropionic acid, House Mice, Shwachman-Bodian-Diamond syndrome, (R)-2-amino-3-mercaptopropanoic acid, CGI-97, 2-Amino-3-mercaptopropionic acid, Laboratory Mice, ME-IV, Protein Gene Products, achromopeptidase, Livers, Gene Proteins, Therapeutic, concentration, Pancreatic insufficiency and bone marrow dysfunction, SCARMD2, E920, Treatment, Peptid, assay, [OH2], Laboratory Mouse, hydrochloric acid, Ultrasonic, skeletal muscle systemfalseProteome analysis of mouse liver and skeletal muscleThe liver and skeletal muscle were collected from 10-week-old wild-type and ob/ob mice fasted for 16 hours. Tissues were frozen immediately and lysed with 0.5 mL of a solution containing 50 mM Tris-HCl pH8.8, 2%SDS, and 7 M urea, and then subjected to ultrasonic treatment with a Bioruptor (Digaenode). The samples were diluted with an equal volume of water and centrifuged at 15,000 g for 15 min at 4°C to remove insoluble fraction. The protein concentration of the lysates was determined with the bicinchoninic acid assay (Thermo Fisher Scientific) and adjusted to 1 mg/mL. Cysteine residues were blocked by incubation of the samples with 2 mM tris(2-carboxyethyl)phosphine hydrochloride (Thermo Fisher Scientific) for 30 min at 37 °C followed by alkylation with 10 mM 2-iodoacetamide for 30 min at room temperature. The proteins (200 µg) were precipitated with acetone for 3 h at −30 °C and the resulting pellet was dispersed in 50 mM Triethylammonium bicarbonate by ultrasonic treatment (three times for 30 s with intervals of 30 s) with a Bioruptor (Diagenode). The protein suspension was subjected to digestion with lysyl endopeptidase (Wako) for 16 h at 37 °C. Resulting peptides were centrifuged at 15,000 g for 15 min at 4°C and subjected to C18-StageTip purification prior to MS analysisWed Mar 03 00:00:00 GMT 2021PXD0206561009033748705