Orexin-A stimulates the expression of GLUT4 in a glucose dependent manner in the liver of orange-spotted grouper (Epinephelus coioides).
Orexins are hypothalamic neuropeptides involved in the central regulation of feeding behavior, sleep-wake cycle and other physiological functions. Orexin-A can regulate energy metabolism and increase glucose uptake, suggesting a role in glucose metabolism. In this study, we investigated the effects of orexin-A on GLUT4 mRNA and protein levels and the intracellular signaling mechanisms mediating orexin-A activity in the hepatocytes of grouper. Our results demonstrate that intraperitoneal injection of orexin-A increased the expression of GLUT4 in the liver, and this effect was significantly enhanced by co-injection of glucose. Treatment of primary cultured hepatocytes with either orexin-A or glucose alone had no effect on the expression of GLUT4, while co-treatment with orexin-A and glucose significantly increased the expression of GLUT4. This stimulatory effect was partially blocked by inhibitors to ERK1/2, JNK or p38 MAPK and was further blocked by an orexin receptor antagonist, which indicates that orexin-A could stimulate the expression of GLUT4 in a glucose dependent manner in primary hepatocytes via ERK1/2, JNK and p38 signaling. Our results suggest that orexin-A could play a pivotal role in stimulating glucose utilization in grouper, for a long-term goal, which might be useful in reducing costs in the aquaculture industry.
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Cong
C
Zhang
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Caiyun
C
Sun
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Bin
B
Wang
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Peipei
P
Yan
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Amin
A
Wu
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
Guokun
G
Yang
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, South China Sea Bio-Resource Exploitation and Collaborative Innovation Center, Research Institute of Sun Yat-Sen University in Shen Zhen, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address: lsslws@mail.sysu.edu.cn.
Wensheng
W
Li
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D000068797:Orexins / Q000008:administration & dosage / Q000494:pharmacology*; D010473:Perciformes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D029941:Fish Proteins; D051275:Glucose Transporter Type 4; D000068797:Orexins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
GLUT4; Glucose; Hepatocytes; Orexin-A; Signaling pathway