title: Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms.
abstract: BACKGROUND
  There is growing evidence that natural products, mostly plant-derived polyphenols, are important in the relationship between nutrients and health in humans.
  
  
  OBJECTIVE
  We aimed to investigate if verbascoside (VB) and other lemon verbena polyphenols could ameliorate obesity-induced metabolic disturbances, as well as their putative mechanism.
  
  
  METHODS
  We used an insulin-resistant hypertrophic 3T3-L1-adipocyte model to test the effects of VB or lemon verbena extract on triglyceride accumulation, inflammation and oxidative stress and a murine model of diet-induced obesity to assess the in vivo metabolic response.
  
  
  RESULTS
  Polyphenols decreased triglyceride accumulation, the generation of reactive oxygen species (ROS) and restored mitochondrial membrane potential in adipocytes. The underlying mechanisms seemed to occur via ROS-mediated downregulation of nuclear factor kappa-B transcription factor (NF-κB) and peroxisome proliferator-activated receptor gamma (PPAR-γ)-dependent transcriptional upregulation of adiponectin. We also observed a potent activation of AMP-activated protein kinase (AMPK), the mRNA expression upregulation of PPAR-α and the mRNA expression downregulation of fatty acid synthase. Experiments in mice suggested a significant improvement in fat metabolism.
  
  
  CONCLUSIONS
  Decreased lipogenesis, enhanced fatty acid oxidation and the activation of the energy sensor AMPK, probably through activating transcriptional factors, are involved in the observed beneficial effects. VB effects were less potent than those observed with the extract, so a potential synergistic, multi-targeted action is proposed. The polypharmacological effects of plant-derived polyphenols from lemon verbena may have the potential for clinical applications in obesity.
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández, Elche, Alicante, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Herranz-López
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández, Elche, Alicante, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Barrajón-Catalán
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.affiliation: Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology and Biomedical Research Institute, Girona, Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menéndez
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, C/ Sant Joan s/n, 43201 Reus, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández, Elche, Alicante, Spain; CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III), Spain. Electronic address: vmicol@umh.es.
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D032411:Lippia / Q000737:chemistry*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology*; D047495:PPAR gamma / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016328:NF-kappa B; D047495:PPAR gamma; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; D054890:Fatty Acid Synthase, Type I; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Adipocyte; Adiponectin; Fat metabolism; Lippia citriodora; Verbascoside