María Herranz-López1, Enrique Barrajón-Catalán1, Antonio Segura-Carretero2, Javier A Menéndez3, Jorge Joven4, Vicente Micol5. 1. Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández, Elche, Alicante, Spain. 2. Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Granada, Spain. 3. Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology and Biomedical Research Institute, Girona, Spain. 4. Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, C/ Sant Joan s/n, 43201 Reus, Spain. 5. 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.
Abstract
BACKGROUND: There is growing evidence that natural products, mostly plant-derived polyphenols, are important in the relationship between nutrients and health in humans. PURPOSE: We aimed to investigate if verbascoside (VB) and other lemon verbena polyphenols could ameliorate obesity-induced metabolic disturbances, as well as their putative mechanism. STUDY DESIGN: 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. CONCLUSION: 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.
BACKGROUND: There is growing evidence that natural products, mostly plant-derived polyphenols, are important in the relationship between nutrients and health in humans. PURPOSE: We aimed to investigate if verbascoside (VB) and other lemon verbenapolyphenols could ameliorate obesity-induced metabolic disturbances, as well as their putative mechanism. STUDY DESIGN: 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. CONCLUSION: 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: Muhammad Imran; Muhammad Sajid Arshad; Masood Sadiq Butt; Joong-Ho Kwon; Muhammad Umair Arshad; Muhammad Tauseef Sultan Journal: Lipids Health Dis Date: 2017-05-02 Impact factor: 3.876
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