Abstract
Leptin augments glucose and lipid metabolism independent of its effect on satiety. Administration of leptin in rodents increases skeletal muscle β-oxidation by activating AMP-activated protein kinase (AMPK). We previously reported that, as hyperleptinemic as obese human subjects, transgenic skinny mice overexpressing leptin in liver (LepTg) exhibit enhanced insulin sensitivity and lipid clearance. To assess skeletal muscle AMPK activity in leptin-sensitive and -insensitive states, we examined phosphorylation of AMPK and its target, acetyl CoA carboxylase (ACC), in muscles from LepTg under dietary modification. Here we show that phosphorylation of AMPK and ACC are chronically augmented in LepTg soleus muscle, with a concomitant increase in the AMP-to-ATP ratio and a significant decrease in tissue triglyceride content. Despite preexisting hyperleptinemia, high-fat diet (HFD)-fed LepTg develop obesity, insulin-resistance, and hyperlipidemia. In parallel, elevated soleus AMPK and ACC phosphorylation in regular diet-fed LepTg is attenuated, and tissue triglyceride content is increased in those given HFD. Of note, substitution of HFD with regular diet causes a robust recovery of soleus AMPK and ACC phosphorylation in LepTg, with a higher rate of body weight reduction and a regain of insulin sensitivity. In conclusion, soleus AMPK and ACC phosphorylation in LepTg changes in parallel with its insulin sensitivity under dietary modification, suggesting a close association between skeletal muscle AMPK activity and sensitivity to leptin.
| Original language | English |
|---|---|
| Pages (from-to) | 2365-2374 |
| Number of pages | 10 |
| Journal | Diabetes |
| Volume | 54 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 1 2005 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification. / Tanaka, Tomohiro; Hidaka, Shuji; Masuzaki, Hiroaki; Yasue, Shintaro; Minokoshi, Yasuhiko; Ebihara, Ken; Chusho, Hideki; Ogawa, Yoshihiro; Toyoda, Taro; Sato, Kenji; Miyanaga, Fumiko; Fujimoto, Muneya; Tomita, Tsutomu; Kusakabe, Toru; Kobayashi, Nozomi; Tanioka, Hideki; Hayashi, Tatsuya; Hosoda, Kiminori; Yoshimatsu, Hironobu; Sakata, Toshiie; Nakao, Kazuwa.
In: Diabetes, Vol. 54, No. 8, 01.08.2005, p. 2365-2374.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skeletal muscle AMP-activated protein kinase phosphorylation parallels metabolic phenotype in leptin transgenic mice under dietary modification
AU - Tanaka, Tomohiro
AU - Hidaka, Shuji
AU - Masuzaki, Hiroaki
AU - Yasue, Shintaro
AU - Minokoshi, Yasuhiko
AU - Ebihara, Ken
AU - Chusho, Hideki
AU - Ogawa, Yoshihiro
AU - Toyoda, Taro
AU - Sato, Kenji
AU - Miyanaga, Fumiko
AU - Fujimoto, Muneya
AU - Tomita, Tsutomu
AU - Kusakabe, Toru
AU - Kobayashi, Nozomi
AU - Tanioka, Hideki
AU - Hayashi, Tatsuya
AU - Hosoda, Kiminori
AU - Yoshimatsu, Hironobu
AU - Sakata, Toshiie
AU - Nakao, Kazuwa
PY - 2005/8/1
Y1 - 2005/8/1
N2 - Leptin augments glucose and lipid metabolism independent of its effect on satiety. Administration of leptin in rodents increases skeletal muscle β-oxidation by activating AMP-activated protein kinase (AMPK). We previously reported that, as hyperleptinemic as obese human subjects, transgenic skinny mice overexpressing leptin in liver (LepTg) exhibit enhanced insulin sensitivity and lipid clearance. To assess skeletal muscle AMPK activity in leptin-sensitive and -insensitive states, we examined phosphorylation of AMPK and its target, acetyl CoA carboxylase (ACC), in muscles from LepTg under dietary modification. Here we show that phosphorylation of AMPK and ACC are chronically augmented in LepTg soleus muscle, with a concomitant increase in the AMP-to-ATP ratio and a significant decrease in tissue triglyceride content. Despite preexisting hyperleptinemia, high-fat diet (HFD)-fed LepTg develop obesity, insulin-resistance, and hyperlipidemia. In parallel, elevated soleus AMPK and ACC phosphorylation in regular diet-fed LepTg is attenuated, and tissue triglyceride content is increased in those given HFD. Of note, substitution of HFD with regular diet causes a robust recovery of soleus AMPK and ACC phosphorylation in LepTg, with a higher rate of body weight reduction and a regain of insulin sensitivity. In conclusion, soleus AMPK and ACC phosphorylation in LepTg changes in parallel with its insulin sensitivity under dietary modification, suggesting a close association between skeletal muscle AMPK activity and sensitivity to leptin.
AB - Leptin augments glucose and lipid metabolism independent of its effect on satiety. Administration of leptin in rodents increases skeletal muscle β-oxidation by activating AMP-activated protein kinase (AMPK). We previously reported that, as hyperleptinemic as obese human subjects, transgenic skinny mice overexpressing leptin in liver (LepTg) exhibit enhanced insulin sensitivity and lipid clearance. To assess skeletal muscle AMPK activity in leptin-sensitive and -insensitive states, we examined phosphorylation of AMPK and its target, acetyl CoA carboxylase (ACC), in muscles from LepTg under dietary modification. Here we show that phosphorylation of AMPK and ACC are chronically augmented in LepTg soleus muscle, with a concomitant increase in the AMP-to-ATP ratio and a significant decrease in tissue triglyceride content. Despite preexisting hyperleptinemia, high-fat diet (HFD)-fed LepTg develop obesity, insulin-resistance, and hyperlipidemia. In parallel, elevated soleus AMPK and ACC phosphorylation in regular diet-fed LepTg is attenuated, and tissue triglyceride content is increased in those given HFD. Of note, substitution of HFD with regular diet causes a robust recovery of soleus AMPK and ACC phosphorylation in LepTg, with a higher rate of body weight reduction and a regain of insulin sensitivity. In conclusion, soleus AMPK and ACC phosphorylation in LepTg changes in parallel with its insulin sensitivity under dietary modification, suggesting a close association between skeletal muscle AMPK activity and sensitivity to leptin.
UR - http://www.scopus.com/inward/record.url?scp=23644455851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644455851&partnerID=8YFLogxK
U2 - 10.2337/diabetes.54.8.2365
DO - 10.2337/diabetes.54.8.2365
M3 - Article
C2 - 16046303
AN - SCOPUS:23644455851
VL - 54
SP - 2365
EP - 2374
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 8
ER -