title: Increased Dynamics of Tricarboxylic Acid Cycle and Glutamate Synthesis in Obese Adipose Tissue: IN VIVO METABOLIC TURNOVER ANALYSIS.
abstract: Obesity is closely associated with various metabolic disorders. However, little is known about abnormalities in the metabolic change of obese adipose tissue. Here we use static metabolic analysis andin vivometabolic turnover analysis to assess metabolic dynamics in obese mice. The static metabolic analyses showed that glutamate and constitutive metabolites of the TCA cycle were increased in the white adipose tissue (WAT) of ob/ob and diet-induced obesity mice but not in the liver or skeletal muscle of these obese mice. Moreover,in vivometabolic turnover analyses demonstrated that these glucose-derived metabolites were dynamically and specifically produced in obese WAT compared with lean WAT. Glutamate rise in obese WAT was associated with down-regulation of glutamate aspartate transporter (GLAST), a major glutamate transporter for adipocytes, and low uptake of glutamate into adipose tissue. In adipocytes, glutamate treatment reduced adiponectin secretion and insulin-mediated glucose uptake and phosphorylation of Akt. These data suggest that a high intra-adipocyte glutamate level potentially relates to adipocyte dysfunction in obesity. This study provides novel insights into metabolic dysfunction in obesity through comprehensive application ofin vivometabolic turnover analysis in two obese animal models.
authors.affiliation: From the Departments of Metabolic Medicine.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nagao
authors.affiliation: From the Departments of Metabolic Medicine, hitoshin1127@endmet.med.osaka-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nishizawa
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yasumune
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Bio-system Pharmacology, and.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Isozumi
authors.affiliation: Bio-system Pharmacology, and.
authors.forename: Shushi
authors.initials: S
authors.lastname: Nagamori
authors.affiliation: Bio-system Pharmacology, and.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: From the Departments of Metabolic Medicine.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: From the Departments of Metabolic Medicine.|Metabolism and Atherosclerosis, Graduate School of Medicine, and.
authors.forename: Shunbun
authors.initials: S
authors.lastname: Kita
authors.affiliation: From the Departments of Metabolic Medicine.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: From the Departments of Metabolic Medicine.|Metabolism and Atherosclerosis, Graduate School of Medicine, and.
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.affiliation: From the Departments of Metabolic Medicine.|Metabolism and Atherosclerosis, Graduate School of Medicine, and.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
authors.affiliation: From the Departments of Metabolic Medicine.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D041721:3T3-L1 Cells; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002952:Citric Acid Cycle; D059305:Diet, High-Fat / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism*
chemical_list: D005971:Glutamates; D005947:Glucose
keywords: adipocyte; adipose tissue metabolism; glutamate; metabolomics; obesity