Ellagic acid in pomegranate suppresses resistin secretion by a novel regulatory mechanism involving the degradation of intracellular resistin protein in adipocytes.
Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. Pomegranate is a rich source of compounds used to treat metabolic diseases including type 2 diabetes. In this study, we found that consumption of pomegranate fruit extract (PFE) predominantly reduced the serum resistin levels in ovariectomized mice, an animal model with elevated resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Moreover, the PFE significantly reduced the secretion and intracellular protein levels of resistin in differentiated murine 3T3-L1 adipocytes, but it did not alter resistin mRNA expression. When de novo protein synthesis was inhibited by the protein synthesis inhibitor cycloheximide, the intracellular resistin protein levels were drastically reduced by the PFE, suggesting that the PFE promoted the degradation of resistin at the protein level. We also found that ellagic acid (EA), a main component of pomegranate, had the same effects on the secretion and intracellular protein level of resistin. These results suggest that EA in pomegranate suppresses resistin secretion by a novel mechanism involving the degradation of intracellular resistin protein in adipocytes.
Department of Applied Biological Chemistry, Graduate School of Agricultural Science, Kinki University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan.
Yasuko
Y
Makino-Wakagi
Yukihiro
Y
Yoshimura
Yuki
Y
Uzawa
Nobuhiro
N
Zaima
Tatsuya
T
Moriyama
Yukio
Y
Kawamura
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004610:Ellagic Acid / Q000494:pharmacology*; D005260:Female; D029561:Lythraceae / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D010936:Plant Extracts / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D052243:Resistin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D010936:Plant Extracts; D011500:Protein Synthesis Inhibitors; D052243:Resistin; D004610:Ellagic Acid; D003513:Cycloheximide