Abstract
In addition to providing skeletal support, the bone is an endocrine organ that produces osteocalcin, whose uncarboxylated form (GluOC) increases insulin secretion either directly or indirectly by promoting incretin secretion. We have now investigated the signaling pathway by which GluOC increases expression of adiponectin in adipocytes. Activation of its putative receptor GPRC6A by GluOC induced the intracellular accumulation of cAMP and consequent activation of protein kinase A (PKA) in differentiated 3T3-L1 adipocytes. It also induced phosphorylation of CREB (cAMP response element binding protein), but this effect appeared to be mediated indirectly by extracellular signal-regulated kinase (ERK) rather than directly by PKA, given that it was attenuated by the ERK signaling inhibitor U0126. Activated PKA also induced activation of the tyrosine kinase Src, the small GTPase Rap1, an upstream of ERK and CREB phosphorylation. Activated CREB up-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), which in turn led to induction of adiponectin expression. Finally, intermittent oral administration of GluOC in mice reduced the size of gonadal white adipocytes as well as increased the expression of PPARγ and adiponectin in these cells. Our results have thus revealed the signaling pathway by which GluOC induces adiponectin expression in adipocytes.
| Original language | English |
|---|---|
| Pages (from-to) | 532-544 |
| Number of pages | 13 |
| Journal | Cellular Signalling |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1 2015 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
Cite this
Signaling pathway for adiponectin expression in adipocytes by osteocalcin. / Otani, Takahito; Mizokami, Akiko; Hayashi, Yoshikazu; Gao, Jing; Mori, Yoshihide; Nakamura, Seiji; Takeuchi, Hiroshi; Hirata, Masato.
In: Cellular Signalling, Vol. 27, No. 3, 01.03.2015, p. 532-544.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Signaling pathway for adiponectin expression in adipocytes by osteocalcin
AU - Otani, Takahito
AU - Mizokami, Akiko
AU - Hayashi, Yoshikazu
AU - Gao, Jing
AU - Mori, Yoshihide
AU - Nakamura, Seiji
AU - Takeuchi, Hiroshi
AU - Hirata, Masato
PY - 2015/3/1
Y1 - 2015/3/1
N2 - In addition to providing skeletal support, the bone is an endocrine organ that produces osteocalcin, whose uncarboxylated form (GluOC) increases insulin secretion either directly or indirectly by promoting incretin secretion. We have now investigated the signaling pathway by which GluOC increases expression of adiponectin in adipocytes. Activation of its putative receptor GPRC6A by GluOC induced the intracellular accumulation of cAMP and consequent activation of protein kinase A (PKA) in differentiated 3T3-L1 adipocytes. It also induced phosphorylation of CREB (cAMP response element binding protein), but this effect appeared to be mediated indirectly by extracellular signal-regulated kinase (ERK) rather than directly by PKA, given that it was attenuated by the ERK signaling inhibitor U0126. Activated PKA also induced activation of the tyrosine kinase Src, the small GTPase Rap1, an upstream of ERK and CREB phosphorylation. Activated CREB up-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), which in turn led to induction of adiponectin expression. Finally, intermittent oral administration of GluOC in mice reduced the size of gonadal white adipocytes as well as increased the expression of PPARγ and adiponectin in these cells. Our results have thus revealed the signaling pathway by which GluOC induces adiponectin expression in adipocytes.
AB - In addition to providing skeletal support, the bone is an endocrine organ that produces osteocalcin, whose uncarboxylated form (GluOC) increases insulin secretion either directly or indirectly by promoting incretin secretion. We have now investigated the signaling pathway by which GluOC increases expression of adiponectin in adipocytes. Activation of its putative receptor GPRC6A by GluOC induced the intracellular accumulation of cAMP and consequent activation of protein kinase A (PKA) in differentiated 3T3-L1 adipocytes. It also induced phosphorylation of CREB (cAMP response element binding protein), but this effect appeared to be mediated indirectly by extracellular signal-regulated kinase (ERK) rather than directly by PKA, given that it was attenuated by the ERK signaling inhibitor U0126. Activated PKA also induced activation of the tyrosine kinase Src, the small GTPase Rap1, an upstream of ERK and CREB phosphorylation. Activated CREB up-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), which in turn led to induction of adiponectin expression. Finally, intermittent oral administration of GluOC in mice reduced the size of gonadal white adipocytes as well as increased the expression of PPARγ and adiponectin in these cells. Our results have thus revealed the signaling pathway by which GluOC induces adiponectin expression in adipocytes.
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UR - http://www.scopus.com/inward/citedby.url?scp=84922649517&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2014.12.018
DO - 10.1016/j.cellsig.2014.12.018
M3 - Article
C2 - 25562427
AN - SCOPUS:84922649517
VL - 27
SP - 532
EP - 544
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 3
ER -