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      The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP-) 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats

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          Abstract

          Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS). We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT) from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV) and quercetin (QRC). We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ when compared to the control group. Furthermore, PPAR-α protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR-γ expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-α expression.

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          Brown and beige fat: development, function and therapeutic potential.

          Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.
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            Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ.

            Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Here we report that gain of function of the NAD-dependent deacetylase SirT1 or loss of function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-γ on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Pparγ, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Pparγ mutant induces a brown phenotype in white adipocytes, whereas an acetylated mimetic fails to induce "brown" genes but retains the ability to activate "white" genes. We propose that SirT1-dependent Pparγ deacetylation is a form of selective Pparγ modulation of potential therapeutic import. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

              Objective Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus, we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). Methods CD1 female mice (5-month-old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. Results Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1), PR domain-containing 16 (PRDM16), Cell death-inducing DFFA-like effector A (Cidea), elongation of very long chain fatty acids protein 3 (Elovl3), peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iWAT stromal vascular cells (SVC), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. Conclusion Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial anti-obesity effects may be partly due to the browning of WAT and as a consequence, increased oxygen consumption.

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 July 2016
                July 2016
                : 17
                : 7
                : 1069
                Affiliations
                [1 ]Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Tlalpan, Mexico City 14080, Mexico; vcastrejn@ 123456yahoo.com.mx (V.C.-T.); gualanv@ 123456yahoo.com (V.G.-L.)
                [2 ]Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Tlalpan, Mexico City 14080, Mexico; josemanuel_rodriguezperez@ 123456yahoo.com.mx (J.M.R.-P.); unicanona@ 123456yahoo.com.mx (N.P.-H.); gvargas63@ 123456yahoo.com (G.V.-A.)
                [3 ]Department of Pathology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Tlalpan, Mexico City 14080, Mexico; pertorisr@ 123456yahoo.com.mx
                [4 ]Department of Immunology Research, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Tlalpan, Mexico City 14080, Mexico; alfredoc1@ 123456gmail.com
                Author notes
                [* ]Correspondence: esther_rubio_ruiz@ 123456yahoo.com ; Tel.: +52-5573-2911 (ext. 1278); Fax: +52-5573-0994
                [†]

                These authors contributed equally to this work.

                Article
                ijms-17-01069
                10.3390/ijms17071069
                4964445
                27399675
                5386530a-8bb1-4233-97e5-e315e977fa17
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 May 2016
                : 28 June 2016
                Categories
                Article

                Molecular biology
                metabolic syndrome,obesity,resveratrol,quercetin,uncoupling proteins
                Molecular biology
                metabolic syndrome, obesity, resveratrol, quercetin, uncoupling proteins

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