p-Synephrine suppresses glucose production but not lipid accumulation in H4IIE liver cells.
p-Synephrine, the primary protoalkaloid in the extract of bitter orange and other citrus species, has gained interest due to its lipolytic activity in adipose tissues. We previously found that p-synephrine stimulates glucose consumption via AMP-activated protein kinase (AMPK) in L6 skeletal muscle cells. This study investigated the effect of p-synephrine on glucose production and lipid accumulation in H4IIE rat liver cells. Glucose production was increased in H4llE cells that were incubated in glucose-free medium but decreased dose dependently (1-100 μM) with p-synephrine treatment. Protein levels of glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase (PEPCK) were also decreased by treatment (4 h) with p-synephrine. Antagonists against α- and β-adrenergic receptors (phentolamine and propranolol) and other inhibitors against signaling molecules did not interrupt p-synephrine-induced suppression in glucose production. However, H7 (an inhibitor of serine/threonine kinases PKA, PKC, and PKG) significantly blocked p-synephrine-induced suppression of glucose production and further increased basal glucose production. Unlike the suppressive effect on glucose production, p-synephrine failed to affect palmitic acid-induced cytoplasmic lipid accumulation. Protein levels of fatty acid synthase (FAS) and phosphorylation levels of AMPK and ACC were not changed by p-synephrine. Altogether, p-synephrine can suppress glucose production but does not affect lipid accumulation in H4IIE liver cells.
1 Department of Histology and Embryology, Hainan Medical University , Haikou, China .
Zhigang
Z
Cui
Youngil
Y
Lee
Youngki
Y
Lee
Deokbae
D
Park
D000818:Animals; D002460:Cell Line; D002957:Citrus / Q000737:chemistry*; D005947:Glucose / Q000096:biosynthesis*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D013578:Synephrine / Q000494:pharmacology*
D010936:Plant Extracts; D005947:Glucose; D013578:Synephrine
H4IIE liver cells; glucose production; lipid accumulation; p-synephrine