Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice
Abstract
:1. Introduction
2. Results
2.1. Oxyresveratrol Decreases Lipid Accumulation and Adipocyte Differentiation
2.2. Oxyresveratrol Prevents Weight Gain and Improves Metabolic Profiles in HFD-Fed Obese Mice
2.3. Oxyresveratrol Increases Energy Expenditure
2.4. Oxyresveratrol Stimulates the Expression of Thermogenic Genes in Adipocytes and Adipose Tissue
2.5. Foxo3a Induced by Oxyresveratrol Stimulates Thermogenic Gene Expression in Adipocytes
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Adipocyte Differentiation
4.2. Cell Viability Assays
4.3. Expression Analysis
4.4. Knockdown and Overexpression Studies
4.5. Animal Studies
4.6. Metabolic Studies
4.7. Temperature Measurements
4.8. Collection of Feces and Extraction of Lipid
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PPARγ | Peroxisome proliferator-activated receptor γ |
Fabp4 | Fatty acid binding protein 4 |
siRNA | Small interfering RNA |
MSC | Mesenchymal stem cells |
DMI | Dexamethasone, IBMX, and Insulin |
AMPK | AMP- activated protein kinase |
Ucp1 | Uncoupling protein1 |
WAT | White adipose tissue |
BAT | Brown adipose tissue |
Myf5 | Myogenic factor (Myf5) |
Pax7 | Paired box 7 |
En1 | Engrailed 1 |
PDGF- β | Platelet-derived growth factor–β |
SMA | Smooth muscle |
Myh11 | Myosin heavy chain 11 |
Prdm16 | PR domain containing protein 16 |
Pgc-1α | Peroxisome proliferator-activated receptor gamma coactivator-1α |
TRPV1 | Transient receptor potential vanilloid 1 |
HFD | High-fat diet |
Foxo3a | Forkhead box o3a |
Retn | Resistin |
Nnmt | Nicotinamide N-Methyltransferase |
Rarres2 | Retinoic acid receptor responder protein 2 |
Cidea | Cell death-inducing DFFA-like effector a |
Elovl3 | Elongation of very long chain fatty acids protein 3 |
Sirt1 | Sirtuin 1 |
Cox7a1 | Cytochrome c oxidase polypeptide 7a1 |
Cox8b | Cytochrome c oxidase subunit 8b |
References
- Hill, J.O.; Peters, J.C. Environmental contributions to the obesity epidemic. Science 1998, 280, 1371–1374. [Google Scholar] [CrossRef] [PubMed]
- Martinez, J.A. Body-weight regulation: Causes of obesity. Proc. Nutr. Soc. 2000, 59, 337–345. [Google Scholar] [CrossRef] [PubMed]
- Lloyd-Jones, D.; Adams, R.; Carnethon, M.; De Simone, G.; Ferguson, T.B.; Flegal, K.; Ford, E.; Furie, K.; Go, A.; Greenlund, K.; et al. Heart disease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009, 119, 480–486. [Google Scholar] [CrossRef] [PubMed]
- Bornfeldt, K.E.; Tabas, I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011, 14, 575–585. [Google Scholar] [CrossRef] [PubMed]
- Rosen, E.D.; Spiegelman, B.M. What We Talk About When We Talk About Fat. Cell 2014, 156, 20–44. [Google Scholar] [CrossRef] [PubMed]
- Harms, M.; Seale, P. Brown and beige fat: Development, function and therapeutic potential. Nat. Med. 2013, 19, 1252–1263. [Google Scholar] [CrossRef] [PubMed]
- Cannon, B.; Nedergaard, J. Brown adipose tissue: Function and physiological significance. Physiol. Rev. 2004, 84, 277–359. [Google Scholar] [CrossRef] [PubMed]
- Zechner, R.; Zimmermann, R.; Eichmann, T.O.; Kohlwein, S.D.; Haemmerle, G.; Lass, A.; Madeo, F. FAT SIGNALS—Lipases and lipolysis in lipid metabolism and signaling. Cell Metab. 2012, 15, 279–291. [Google Scholar] [CrossRef] [PubMed]
- Matsuzawa, Y. The metabolic syndrome and adipocytokines. FEBS Lett. 2006, 580, 2917–2921. [Google Scholar] [CrossRef] [Green Version]
- Van Marken Lichtenbelt, W.D.; Vanhommerig, J.W.; Smulders, N.M.; Drossaerts, J.M.; Kemerink, G.J.; Bouvy, N.D.; Schrauwen, P.; Teule, G.J. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 2009, 360, 1500–1508. [Google Scholar] [CrossRef]
- Cypess, A.M.; Weiner, L.S.; Roberts-Toler, C.; Elia, E.F.; Kessler, S.H.; Kahn, P.A.; English, J.; Chatman, K.; Trauger, S.A.; Doria, A.; et al. Activation of Human Brown Adipose Tissue by a beta 3-Adrenergic Receptor Agonist. Cell Metab. 2015, 21, 33–38. [Google Scholar] [CrossRef] [PubMed]
- Symonds, M.E.; Pope, M.; Budge, H. The Ontogeny of Brown Adipose Tissue. Annu. Rev. Nutr. 2015, 35, 295–320. [Google Scholar] [CrossRef] [PubMed]
- Wang, W.; Seale, P. Control of brown and beige fat development. Nat. Rev. Mol. Cell Biol. 2016, 17, 691–702. [Google Scholar] [CrossRef] [PubMed]
- Song, N.J.; Chang, S.H.; Li, D.Y.; Villanueva, C.J.; Park, K.W. Induction of thermogenic adipocytes: Molecular targets and thermogenic small molecules. Exp. Mol. Med. 2017, 49, e353. [Google Scholar] [CrossRef] [PubMed]
- Chao, J.; Yu, M.S.; Ho, Y.S.; Wang, M.; Chang, R.C. Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic. Biol. Med. 2008, 45, 1019–1026. [Google Scholar] [CrossRef] [PubMed]
- Jo, S.P.; Kim, J.K.; Lim, Y.H. Antihyperlipidemic effects of stilbenoids isolated from Morus alba in rats fed a high-cholesterol diet. Food Chem. Toxicol. 2014, 65, 213–218. [Google Scholar] [CrossRef]
- Choi, H.Y.; Lee, J.H.; Jegal, K.H.; Cho, I.J.; Kim, Y.W.; Kim, S.C. Oxyresveratrol abrogates oxidative stress by activating ERK-Nrf2 pathway in the liver. Chem. Biol. Interact. 2016, 245, 110–121. [Google Scholar] [CrossRef]
- Tan, H.Y.; Tse, I.M.; Li, E.T.; Wang, M. Oxyresveratrol Supplementation to C57bl/6 Mice Fed with a High-Fat Diet Ameliorates Obesity-Associated Symptoms. Nutrients 2017, 9, 147. [Google Scholar] [CrossRef]
- Meydani, M.; Hasan, S.T. Dietary polyphenols and obesity. Nutrients 2010, 2, 737–751. [Google Scholar] [CrossRef]
- Andrabi, S.A.; Spina, M.G.; Lorenz, P.; Ebmeyer, U.; Wolf, G.; Horn, T.F. Oxyresveratrol (trans-2,3′,4,5′-tetrahydroxystilbene) is neuroprotective and inhibits the apoptotic cell death in transient cerebral ischemia. Brain Res. 2004, 1017, 98–107. [Google Scholar] [CrossRef]
- Deng, H.; He, X.; Xu, Y.; Hu, X. Oxyresveratrol from Mulberry as a dihydrate. Acta. Crystallogr. Sect. E. Struct. Rep. Online 2012, 68, o1318–o1319. [Google Scholar] [CrossRef] [PubMed]
- Chung, K.O.; Kim, B.Y.; Lee, M.H.; Kim, Y.R.; Chung, H.Y.; Park, J.H.; Moon, J.O. In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J. Pharm. Pharmacol. 2003, 55, 1695–1700. [Google Scholar] [CrossRef] [PubMed]
- Chuanasa, T.; Phromjai, J.; Lipipun, V.; Likhitwitayawuid, K.; Suzuki, M.; Pramyothin, P.; Hattori, M.; Shiraki, K. Anti-herpes simplex virus (HSV-1) activity of oxyresveratrol derived from Thai medicinal plant: Mechanism of action and therapeutic efficacy on cutaneous HSV-1 infection in mice. Antiviral Res. 2008, 80, 62–70. [Google Scholar] [CrossRef] [PubMed]
- Aftab, N.; Likhitwitayawuid, K.; Vieira, A. Comparative antioxidant activities and synergism of resveratrol and oxyresveratrol. Nat. Prod. Res. 2010, 24, 1726–1733. [Google Scholar] [CrossRef] [PubMed]
- Bartelt, A.; Heeren, J. Adipose tissue browning and metabolic health. Nat. Rev. Endocrinol. 2014, 10, 24–36. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Liang, X.; Yang, Q.; Fu, X.; Zhu, M.; Rodgers, B.D.; Jiang, Q.; Dodson, M.V.; Du, M. Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) alpha1 in mice fed high-fat diet. Mol. Nutr. Food Res. 2017, 61, 1600746. [Google Scholar] [CrossRef] [PubMed]
- Van Dam, A.D.; Nahon, K.J.; Kooijman, S.; van den Berg, S.M.; Kanhai, A.A.; Kikuchi, T.; Heemskerk, M.M.; van Harmelen, V.; Lombes, M.; van den Hoek, A.M.; et al. Salsalate activates brown adipose tissue in mice. Diabetes 2015, 64, 1544–1554. [Google Scholar] [CrossRef] [PubMed]
- Qiang, L.; Wang, L.; Kon, N.; Zhao, W.; Lee, S.; Zhang, Y.; Rosenbaum, M.; Zhao, Y.; Gu, W.; Farmer, S.R.; et al. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma. Cell 2012, 150, 620–632. [Google Scholar] [CrossRef]
- Zhang, K.; Guo, W.; Yang, Y.; Wu, J. JAK2/STAT3 pathway is involved in the early stage of adipogenesis through regulating C/EBPbeta transcription. J. Cell. Biochem. 2011, 112, 488–497. [Google Scholar] [CrossRef]
- Sears, I.B.; MacGinnitie, M.A.; Kovacs, L.G.; Graves, R.A. Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: Regulation by peroxisome proliferator-activated receptor gamma. Mol. Cell. Biol. 1996, 16, 3410–3419. [Google Scholar] [CrossRef]
- Seale, P.; Bjork, B.; Yang, W.; Kajimura, S.; Chin, S.; Kuang, S.; Scime, A.; Devarakonda, S.; Conroe, H.M.; Erdjument-Bromage, H.; et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008, 454, 961–967. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Uldry, M.; Yang, W.L.; St-Pierre, J.; Lin, J.D.; Seale, P.; Spiegelman, B.M. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab. 2006, 3, 333–341. [Google Scholar] [CrossRef]
- Ohno, H.; Shinoda, K.; Spiegelman, B.M.; Kajimura, S. PPAR gamma agonists Induce a White-to-Brown Fat Conversion through Stabilization of PRDM16 Protein. Cell Metab. 2012, 15, 395–404. [Google Scholar] [CrossRef] [PubMed]
- Villanueva, C.J.; Vergnes, L.; Wang, J.; Drew, B.G.; Hong, C.; Tu, Y.; Hu, Y.; Peng, X.; Feng, X.; Saez, E.; et al. Adipose Subtype-Selective Recruitment of TLE3 or Prdm16 by PPAR gamma Specifies Lipid Storage versus Thermogenic Gene Programs. Cell Metab. 2013, 17, 423–435. [Google Scholar] [CrossRef] [PubMed]
- Rajakumari, S.; Wu, J.; Ishibashi, J.; Lim, H.W.; Giang, A.H.; Won, K.J.; Reed, R.R.; Seale, P. EBF2 determines and maintains brown adipocyte identity. Cell Metab. 2013, 17, 562–574. [Google Scholar] [CrossRef] [PubMed]
- Song, N.J.; Choi, S.; Rajbhandari, P.; Chang, S.H.; Kim, S.; Vergnes, L.; Kwon, S.M.; Yoon, J.H.; Lee, S.; Ku, J.M.; et al. Prdm4 induction by the small molecule butein promotes white adipose tissue browning. Nat. Chem. Biol. 2016, 12, 479–481. [Google Scholar] [CrossRef] [Green Version]
- Nakae, J.; Cao, Y.; Oki, M.; Orba, Y.; Sawa, H.; Kiyonari, H.; Iskandar, K.; Suga, K.; Lombes, M.; Hayashi, Y. Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure. Diabetes 2008, 57, 563–576. [Google Scholar] [CrossRef]
- Szkudelska, K.; Szkudelski, T. Resveratrol, obesity and diabetes. Eur. J. Pharmacol. 2010, 635, 1–8. [Google Scholar] [CrossRef]
- Andrade, J.M.; Frade, A.C.; Guimaraes, J.B.; Freitas, K.M.; Lopes, M.T.; Guimaraes, A.L.; de Paula, A.M.; Coimbra, C.C.; Santos, S.H. Resveratrol increases brown adipose tissue thermogenesis markers by increasing SIRT1 and energy expenditure and decreasing fat accumulation in adipose tissue of mice fed a standard diet. Eur. J. Nutr. 2014, 53, 1503–1510. [Google Scholar] [CrossRef]
- Lorenz, P.; Roychowdhury, S.; Engelmann, M.; Wolf, G.; Horn, T.F. Oxyresveratrol and resveratrol are potent antioxidants and free radical scavengers: Effect on nitrosative and oxidative stress derived from microglial cells. Nitric Oxide 2003, 9, 64–76. [Google Scholar] [CrossRef]
- Fisher, F.M.; Kleiner, S.; Douris, N.; Fox, E.C.; Mepani, R.J.; Verdeguer, F.; Wu, J.; Kharitonenkov, A.; Flier, J.S.; Maratos-Flier, E.; et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 2012, 26, 271–281. [Google Scholar] [CrossRef] [PubMed]
- Park, K.W.; Waki, H.; Choi, S.P.; Park, K.M.; Tontonoz, P. The small molecule phenamil is a modulator of adipocyte differentiation and PPARgamma expression. J. Lipid Res. 2010, 51, 2775–2784. [Google Scholar] [CrossRef] [PubMed]
- Song, N.J.; Yoon, H.J.; Kim, K.H.; Jung, S.R.; Jang, W.S.; Seo, C.R.; Lee, Y.M.; Kweon, D.H.; Hong, J.W.; Lee, J.S.; et al. Butein is a novel anti-adipogenic compound. J. Lipid Res. 2013, 54, 1385–1396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Folch, J.; Lees, M.; Sloane Stanley, G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957, 226, 497–509. [Google Scholar] [PubMed]
© 2018 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/).
Share and Cite
Choi, J.H.; Song, N.-J.; Lee, A.R.; Lee, D.H.; Seo, M.-J.; Kim, S.; Chang, S.-H.; Yang, D.K.; Hwang, Y.-J.; Hwang, K.-A.; et al. Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice. Int. J. Mol. Sci. 2019, 20, 26. https://doi.org/10.3390/ijms20010026
Choi JH, Song N-J, Lee AR, Lee DH, Seo M-J, Kim S, Chang S-H, Yang DK, Hwang Y-J, Hwang K-A, et al. Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice. International Journal of Molecular Sciences. 2019; 20(1):26. https://doi.org/10.3390/ijms20010026
Chicago/Turabian StyleChoi, Jin Hee, No-Joon Song, A Reum Lee, Dong Ho Lee, Min-Ju Seo, Suji Kim, Seo-Hyuk Chang, Dong Kwon Yang, Yu-Jin Hwang, Kyung-A Hwang, and et al. 2019. "Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice" International Journal of Molecular Sciences 20, no. 1: 26. https://doi.org/10.3390/ijms20010026