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 and in vivo metabolic 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 vivo metabolic 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 of in vivo metabolic turnover analysis in two obese animal models.
| Original language | English |
|---|---|
| Pages (from-to) | 4469-4483 |
| Number of pages | 15 |
| Journal | Journal of Biological Chemistry |
| Volume | 292 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Mar 17 2017 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Increased dynamics of tricarboxylic acid cycle and glutamate synthesis in obese adipose tissue : In vivo metabolic turnover analysis. / Nagao, Hirofumi; Nishizawa, Hitoshi; Bamba, Takeshi; Nakayama, Yasumune; Isozumi, Noriyoshi; Nagamori, Shushi; Kanai, Yoshikatsu; Tanaka, Yoshimitsu; Kita, Shunbun; Fukuda, Shiro; Funahashi, Tohru; Maeda, Norikazu; Fukusaki, Eiichiro; Shimomura, Iichiro.
In: Journal of Biological Chemistry, Vol. 292, No. 11, 17.03.2017, p. 4469-4483.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased dynamics of tricarboxylic acid cycle and glutamate synthesis in obese adipose tissue
T2 - In vivo metabolic turnover analysis
AU - Nagao, Hirofumi
AU - Nishizawa, Hitoshi
AU - Bamba, Takeshi
AU - Nakayama, Yasumune
AU - Isozumi, Noriyoshi
AU - Nagamori, Shushi
AU - Kanai, Yoshikatsu
AU - Tanaka, Yoshimitsu
AU - Kita, Shunbun
AU - Fukuda, Shiro
AU - Funahashi, Tohru
AU - Maeda, Norikazu
AU - Fukusaki, Eiichiro
AU - Shimomura, Iichiro
PY - 2017/3/17
Y1 - 2017/3/17
N2 - 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 and in vivo metabolic 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 vivo metabolic 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 of in vivo metabolic turnover analysis in two obese animal models.
AB - 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 and in vivo metabolic 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 vivo metabolic 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 of in vivo metabolic turnover analysis in two obese animal models.
UR - http://www.scopus.com/inward/record.url?scp=85015337862&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85015337862&partnerID=8YFLogxK
U2 - 10.1074/jbc.M116.770172
DO - 10.1074/jbc.M116.770172
M3 - Article
C2 - 28119455
AN - SCOPUS:85015337862
VL - 292
SP - 4469
EP - 4483
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 11
ER -