title: Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.
abstract: OBJECTIVE
  Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes.
  
  
  METHODS
  We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined.
  
  
  RESULTS
  As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation.
  
  
  CONCLUSIONS
  In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Diana N
authors.initials: DN
authors.lastname: Obanda
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Richard
authors.affiliation: Department of Plant Biology, Rutgers University, New Brunswick, New Jersey, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Ribnicky
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, United States of America.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Stephens
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D055572:Ceramidases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D017343:Genes, Plant; D007328:Insulin / Q000378:metabolism; D051379:Mice; D019308:Palmitic Acid / Q000737:chemistry; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D026982:Urtica dioica / Q000737:chemistry*
chemical_list: D052242:Adiponectin; D002518:Ceramides; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010936:Plant Extracts; D034741:RNA, Small Interfering; D019308:Palmitic Acid; D000431:Ethanol; D055572:Ceramidases