Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models
<p>Reduction of M1 polarization and production of pro-inflammatory cytokines in Raw 264.7 cells, and of adipogensis/lipogenesis in 3T3L-1 cells by PPB from E. cava mRNA levels of (<b>A</b>) CD11b as a general macrophage marker, (<b>B</b>) CD86 as a marker of M1 macrophages, (<b>C</b>) CD206 as a marker of M2 macrophages, (<b>D</b>) TNF-α, and (<b>E</b>) IL-6 in Raw 264.7 cells were measured by qRT-PCR. Cells were pre-treated PA-BSA (0.25 mM) and four phlorotannins (DK, PHB, PFFA, and PPB) for 48 h. mRNA levels of (<b>F</b>) PPARγ, (<b>G</b>) ACC (adipogenesis-related markers), and (<b>H</b>) FAS (lipogenesis-related marker) in PA-BSA (0.25 mM) treated 3T3L-1 cells were measured by qRT-PCR. All mRNA levels are expressed as relative levels and are normalized to β-actin in the BSA group. Significance represented as **, <span class="html-italic">p</span> < 0.01 versus BSA; <span>$</span>, <span class="html-italic">p</span> < 0.05 and <span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.01 versus PA-BSA; #, <span class="html-italic">p</span> < 0.05 and ##, <span class="html-italic">p</span> < 0.01 versus PA-PPB. DK, dieckol; PHB, 2,7-phloroglucinol-6,6-bieckol, PFFA, phlorofucofuroeckol A; PPB, pyrogallol-phloroglucinol-6,6-bieckol; PA-BSA, palmitic acid–conjugated bovine serum albumin.</p> "> Figure 2
<p>Reduction of activated macrophage infiltration, M1 polarization, and pro-inflammatory cytokine production, in the visceral fat and brain of the high fat diet–induced obese mice by PPB from <span class="html-italic">E. cava</span>. Three groups of diet-induced obese (DIO) mice were examined: normal fat diet with saline administration (NFD-Saline, white color), a high fat diet with saline administration (HFD-Saline, orange color), and HFD with PPB (2.5 mg/kg/day) administration (HFD-PPB). Saline and PPB were administered orally. mRNA levels of (<b>A</b>) CD11b as a general macrophage marker, CD86 as a marker of M1 macrophages, and CD206 as a marker of M2 macrophages, and (<b>B</b>) TNF-α and IL-6 in visceral fat tissue were measured by qRT-PCR. mRNA levels of (<b>C</b>) CD11b, CD86, and CD206 as a marker of M2 macrophages, and (<b>D</b>) TNF-α and IL-6 in brain were measured by qRT-PCR. All mRNA levels are expressed as relative levels normalized to β-actin of the NFD-Saline group. Significance represented as *, <span class="html-italic">p</span> < 0.05 and **, <span class="html-italic">p</span> < 0.01 versus NFD-Saline; <span>$</span>, <span class="html-italic">p</span> < 0.05 and <span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.01 versus HFD-Saline. PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> "> Figure 3
<p>Reduction of activated macrophage infiltration, M1 polarization, and pro-inflammatory cytokine production in the visceral fat and brain of the ob/ob mice by PPB from <span class="html-italic">E. cava.</span> Three groups of leptin-deficient obese (ob/ob) mice and wild type (WT) control C57BL/6N mice were examined: Saline orally administered to WT (WT-Saline, white color) or ob/ob mice (ob/ob-Saline, green color). PPB (2.5 mg/kg/day, i.o., ob/ob-PPB), or leptin (0.85 mg/kg/day, i.p., ob/ob-Leptin) was administered to ob/ob mice. mRNA levels of (<b>A</b>) CD11b (general macrophage marker), CD86 (a marker of M1 macrophages), and CD206 (a marker of M2 macrophages) in visceral fat tissue and (<b>B</b>) TNF-α and IL-6 in the visceral fat tissue of were measured by qRT-PCR. mRNA levels of (<b>C</b>) CD11b, CD86, and CD206 in brain and (<b>D</b>) TNF-α and IL-6 in brain of were measured by qRT-PCR. All mRNA levels are expressed as relative levels normalized to β-actin of the WT-Saline group. Significance represented as **, <span class="html-italic">p</span> < 0.01 versus WT-Saline; <span>$</span>, <span class="html-italic">p</span> < 0.05 and <span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.01 versus ob/ob-Saline; #, <span class="html-italic">p</span> < 0.05 and ##, <span class="html-italic">p</span> < 0.01 versus ob/ob-PPB. PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> "> Figure 4
<p>Reduction in TLR4 expression and endoplasmic reticulum (ER) stress in the brain of high fat diet–induced obese mice and ob/ob mice by PPB from <span class="html-italic">E. cava</span> mRNA levels of (<b>A</b>) TLR4 and the ER stress–related molecules including (<b>B</b>) PERK, (<b>C</b>) eIF2α, (<b>D</b>) IRE1, and (<b>E</b>) Xbp1 in the brain of high fat diet–induced obese mice (<b>A–E</b>) and (<b>F</b>) ob/ob mice were measured by qRT-PCR. mRNA levels of (<b>F</b>) TLR4 and the ER stress–related molecules including (<b>G</b>) PERK, (<b>H</b>) eIF2α, (<b>I</b>) IRE1, and (<b>J</b>) Xbp1 in the brain of (<b>F–J</b>) ob/ob mice were measured by qRT-PCR. All mRNA levels were expressed as relative levels normalized to β-actin of the NFD-Saline for high fat diet-induced obese mice group or WT-Saline for ob/ob mice. Significance represented as **, <span class="html-italic">p</span> < 0.01 versus NFD-Saline or WT-Saline; <span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.01 versus HFD-Saline or ob/ob-Saline; ##, <span class="html-italic">p</span> < 0.01 versus ob/ob-PPB. TLR4, Toll-like receptor 4; PERK, protein kinase R (PKR)-like ER protein kinase; eIF2α, eukaryotic initiation factor 2 alpha; IRE1, inositol-requiring protein 1 alpha; Xbp1, X-box–binding protein 1; PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> "> Figure 5
<p>Modulation of NF-κB, SOCS3, pSTAT3, and Ob-R protein levels in the brain of high fat diet–induced obese mice and ob/ob mice by PPB <span class="html-italic">from E. cava</span> (<b>A</b>) NF-κB, (<b>C</b>) SOCS3, STAT3, and phosphorylated STAT3 (pSTAT3) and (<b>E</b>) Ob-R in the brain of high fat diet-induced obese. (<b>B</b>) NF-κB, (<b>D</b>) SOCS3, STAT3, and phosphorylated STAT3 (pSTAT3) and (<b>F</b>) Ob-R in the brain of ob/ob mice. Each protein level was determined by immunoblotting. NF-κB, nuclear factor-kappa B; SOCS3, suppressor of cytokine signaling 3; PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> "> Figure 6
<p>Reduction of adipogenesis and lipogenesis-related molecule expression in the brain of high fat diet-induced obese mice and ob/ob mice by PPB <span class="html-italic">from E. cava</span> mRNA levels of the adipogenesis-related molecules (<b>A</b>) PPARγ and CEBP, and lipogenesis-related molecules (<b>B</b>) ACC and FAS in the brain of high fat diet–induced obese mice were measured by qRT-PCR and (<b>C</b>) PPARγ and CEBP, and lipogenesis-related molecules (<b>D</b>) ACC and FAS in the brain of ob/ob mice were measured by qRT-PCR. All mRNA levels are expressed as relative levels normalized to β-actin of the NFD-Saline for high fat diet-induced obese mice group or WT-Saline for ob/ob mice. Significance represented as **, <span class="html-italic">p</span> < 0.01 versus NFD-Saline or WT-Saline; <span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.01 versus HFD-Saline or ob/ob-Saline; #, <span class="html-italic">p</span> < 0.05 and ##, <span class="html-italic">p</span> < 0.01 versus ob/ob-PPB. PPARγ, peroxisome proliferator-activated receptor gamma; CEBP, CCAAT enhancer–binding protein; ACC, acetyl-CoA carboxylase; FAS, fatty acid synthase; PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> "> Figure 7
<p>Reduction of body weight, food intake, and visceral fat size in high fat diet-induced obese mice and ob/ob mice by PPB from <span class="html-italic">E. cava</span> (<b>A</b>) Body weight, body composition (fat mass and lean mass), and (<b>B</b>) food intake of high fat diet–induced obese mice were measured before sacrifice. (<b>C</b>) Visceral fat was stained with hematoxylin and eosin (H&E). (<b>D</b>) Body weight, body composition (fat mass and lean mass), and (<b>E</b>) food intake of ob/ob mice were measured before sacrifice. (<b>F</b>) Visceral fat was stained with H&E. The size of the cells was quantified using Image J software and is shown as a graph. Scale bar = 50 µm. Significance represented as ***, <span class="html-italic">p</span> < 0.001 versus NFD-Saline or WT-Saline; <span>$</span><span>$</span><span>$</span>, <span class="html-italic">p</span> < 0.001 versus HFD-Saline or ob/ob-Saline; ##, <span class="html-italic">p</span> < 0.01 versus ob/ob-PPB. PPB, pyrogallol-phloroglucinol-6,6-bieckol.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Preparation of Palmitic Acid–Conjugated Bovine Serum Albumin and Cell Treatment
2.3. Animals
2.3.1. High-Fat-Diet-Induced Obese Mice
2.3.2. Leptin-Deficient Mice
2.4. Isolation of Compounds from E. cava Extract
2.5. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)
2.6. Immunoblotting
2.7. Fat size Analysis
2.8. Statistical Analysis
3. Results
3.1. PPB Decreases M1 Polarization and Production of Inflammatory Cytokines in Raw 264.7 Cells, and Decreases Adipogenesis and Lipogenesis in 3t3l-1 Cells More Efficiently than Other Components of E. cava Extracts
3.2. PPB Reduces Activated Macrophage Infiltration, M1 Polarization, and Inflammatory Cytokine Expression Levels in the Adipose Tissue and Brain of High Fat Diet–Induced Obese Mice
3.3. PPB Reduces Activated Macrophage Infiltration, M1 Polarization, and Inflammatory Cytokine Transcript Levels in the Adipose Tissue and Brain of Ob/Ob Mice
3.4. PPB Attenuates TLR4 Expression and Endoplasmic Reticulum (ER) Stress in the Brain of DIO and Ob/Ob Mice
3.5. PPB Decreases the NF-κB Level in the Brain of DIO and Ob/Ob Mice
3.6. PPB Attenuates Leptin Resistance in the Brain of DIO Mice
3.7. PPB Increases Leptin Sensitivity in the Brain of Ob/Ob Mice
3.8. PPB Decreases Adipogenesis and Lipogenesis in the Adipose Tissue of DIO and Ob/Ob Mice
3.9. PPB Decreases Body Weight Gain, Fat Mass, Food Intake, and Visceral Fat Size
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviation
References
- Wauman, J.; Zabeau, L.; Tavernier, J. The leptin receptor complex: Heavier than expected? Front. Endocrinol. 2017, 8, 30. [Google Scholar] [CrossRef] [PubMed]
- Considine, R.V.; Sinha, M.K.; Heiman, M.L.; Kriauciunas, A.; Stephens, T.W.; Nyce, M.R.; Ohannesian, J.P.; Marco, C.C.; McKee, L.J.; Bauer, T.L.; et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med. 1996, 334, 292–295. [Google Scholar] [CrossRef] [PubMed]
- Rizwan, M.Z.; Mehlitz, S.; Grattan, D.R.; Tups, A. Temporal and regional onset of leptin resistance in diet-induced obese mice. J. Neuroendocrinol. 2017, 29, e12481. [Google Scholar] [CrossRef] [PubMed]
- Campfield, L.A.; Smith, F.J.; Guisez, Y.; Devos, R.; Burn, P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 1995, 269, 546–549. [Google Scholar] [CrossRef] [PubMed]
- Myers, M.G., Jr.; Leibel, R.L.; Seeley, R.J.; Schwartz, M.W. Obesity and leptin resistance: Distinguishing cause from effect. Trends Endocrinol. Metab. 2010, 21, 643–651. [Google Scholar] [CrossRef]
- Ladyman, S.R.; Grattan, D.R. Region-specific reduction in leptin-induced phosphorylation of signal transducer and activator of transcription-3 (STAT3) in the rat hypothalamus is associated with leptin resistance during pregnancy. Endocrinology 2004, 145, 3704–3711. [Google Scholar] [CrossRef]
- Münzberg, H.; Flier, J.S.; Bjørbaek, C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 2004, 145, 4880–4889. [Google Scholar] [CrossRef]
- Bjørbaek, C.; Elmquist, J.K.; Frantz, J.D.; Shoelson, S.E.; Flier, J.S. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol. Cell 1998, 1, 619–625. [Google Scholar] [CrossRef]
- Thaler, J.P.; Yi, C.X.; Schur, E.A.; Guyenet, S.J.; Hwang, B.H.; Dietrich, M.O.; Zhao, X.; Sarruf, D.A.; Izgur, V.; Maravilla, K.R.; et al. Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest 2012, 122, 153–162. [Google Scholar] [CrossRef]
- Jernås, M.; Palming, J.; Sjöholm, K.; Jennische, E.; Svensson, P.A.; Gabrielsson, B.G.; Levin, M.; Sjögren, A.; Rudemo, M.; Lystig, T.C.; et al. Separation of human adipocytes by size: Hypertrophic fat cells display distinct gene expression. FASEB J. 2006, 20, 1540–1542. [Google Scholar] [CrossRef]
- Choe, S.S.; Huh, J.Y.; Hwang, I.J.; Kim, J.I.; Kim, J.B. Adipose tissue remodeling: Its role in energy metabolism and metabolic disorders. Front. Endocrinol. (Lausanne) 2016, 7, 30. [Google Scholar] [CrossRef] [PubMed]
- De Git, K.C.; Adan, R.A. Leptin resistance in diet-induced obesity: The role of hypothalamic inflammation. Obes. Rev. 2015, 16, 207–224. [Google Scholar] [CrossRef] [PubMed]
- Ropelle, E.R.; Flores, M.B.; Cintra, D.E.; Rocha, G.Z.; Pauli, J.R.; Morari, J.; de Souza, C.T.; Moraes, J.C.; Prada, P.O.; Guadagnini, D.; et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKβ and ER stress inhibition. PLoS Biol. 2010, 8, e1000465. [Google Scholar] [CrossRef] [PubMed]
- Oh-I, S.; Shimizu, H.; Sato, T.; Uehara, Y.; Okada, S.; Mori, M. Molecular mechanisms associated with leptin resistance: N-3 polyunsaturated fatty acids induce alterations in the tight junction of the brain. Cell Metab. 2005, 1, 331–341. [Google Scholar] [CrossRef]
- Zhang, X.; Zhang, G.; Zhang, H.; Karin, M.; Bai, H.; Cai, D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008, 135, 61–73. [Google Scholar] [CrossRef]
- Mendes, N.F.; Kim, Y.B.; Velloso, L.A.; Araújo, E.P. Hypothalamic microglial activation in obesity: A mini-review. Front. Neurosci. 2018, 12, 846. [Google Scholar] [CrossRef]
- Tang, Y.; Le, W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol. 2016, 53, 1181–1194. [Google Scholar] [CrossRef]
- Oh, S.; Son, M.; Lee, H.S.; Kim, H.; Jeon, Y.J.; Byun, K. Protective effect of pyrogallol-phloroglucinol-6,6-bieckol from Ecklonia cava on monocyte-associated vascular dysfunction. Mar. Drugs 2018, 16, 441. [Google Scholar] [CrossRef]
- Li, Y.; Qian, Z.J.; Ryu, B.; Lee, S.H.; Kim, M.M.; Kim, S.K. Chemical components and its antioxidant properties in vitro: An edible marine brown alga, Ecklonia cava. Bioorg. Med. Chem. 2009, 17, 1963–1973. [Google Scholar] [CrossRef]
- Kang, C.; Jin, Y.B.; Lee, H.; Cha, M.; Sohn, E.T.; Moon, J.; Park, C.; Chun, S.; Jung, E.S.; Hong, J.S.; et al. Brown alga Ecklonia cava attenuates type 1 diabetes by activating AMPK and Akt signaling pathways. Food Chem. Toxicol. 2010, 48, 509–516. [Google Scholar] [CrossRef]
- Lee, S.H.; Han, J.S.; Heo, S.J.; Hwang, J.Y.; Jeon, Y.J. Protective effects of dieckol isolated from Ecklonia cava against high glucose-induced oxidative stress in human umbilical vein endothelial cells. Toxicol. In Vitro 2010, 24, 375–381. [Google Scholar] [CrossRef] [PubMed]
- Son, M.; Oh, S.; Lee, H.S.; Ryu, B.; Jiang, J.T.; Jeon, Y.J.; Byun, K.H. Pyrogallol-phloroglucinol-6,6’-bieckol from Ecklonia cava improved blood circulation in diet-induced obese and diet-induced hypertension mouse models. Mar. Drugs 2019, 17, 272. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.H.; Ko, J.Y.; Oh, J.Y.; Kim, C.Y.; Lee, H.J.; Kim, J.; Jeon, Y.J. Preparative isolation and purification of phlorotannins from Ecklonia cava using centrifugal partition chromatography by one-step. Food Chem. 2014, 158, 433–437. [Google Scholar] [CrossRef] [PubMed]
- Roy, N.H.; Lambelé, M.; Chan, J.; Symeonides, M.; Thali, M. Ezrin is a component of the HIV-1 virologicalpresynapse and contributes to the inhibition of cell-cell fusion. J. Virol. 2014, 88, 7645–7658. [Google Scholar] [CrossRef] [PubMed]
- Le Thuc, O.; Stobbe, K.; Cansell, C.; Nahon, J.L.; Blondeau, N.; Rovère, C. Hypothalamic inflammation and energy balance disruptions: Spotlight on chemokines. Front. Endocrinol. 2017, 8, 197. [Google Scholar] [CrossRef] [PubMed]
- Valdearcos, M.; Robblee, M.M.; Benjamin, D.I.; Nomura, D.K.; Xu, A.W.; Koliwad, S.K. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 2014, 9, 2124–2138. [Google Scholar] [CrossRef] [PubMed]
- Milanski, M.; Degasperi, G.; Coope, A.; Morari, J.; Denis, R.; Cintra, D.E.; Tsukumo, D.M.; Anhe, G.; Amaral, M.E.; Takahashi, H.K.; et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: Implications for the pathogenesis of obesity. J. Neurosci. 2009, 29, 359–370. [Google Scholar] [CrossRef]
- Wang, X.; Ge, A.; Cheng, M.; Guo, F.; Zhao, M.; Liu, L.; Yang, N. Increased hypothalamic inflammation associated with the susceptibility to obesity in rats exposed to high-fat diet. Exp. Diabetes Res. 2012, 2012, 847246. [Google Scholar] [CrossRef]
- Yao, L.; Kan, E.M.; Lu, J.; Hao, A.; Dheen, S.T.; Kaur, C.; Ling, E.A. Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: Role of TLR4 in hypoxic microglia. J. Neuroinflammation 2013, 10, 23–43. [Google Scholar] [CrossRef]
- Li, X. Endoplasmic reticulum stress regulates inflammation in adipocyte of obese rats via toll-like receptors 4 signaling. Iran. J. Basic Med. Sci. 2018, 21, 502–507. [Google Scholar]
- Romanatto, T.; Cesquini, M.; Amaral, M.E.; Roman, E.A.; Moraes, J.C.; Torsoni, M.A.; Cruz-Neto, A.P.; Velloso, L.A. TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient—Effects on leptin and insulin signaling. Peptides 2007, 28, 1050–1058. [Google Scholar] [CrossRef] [PubMed]
- Santoro, A.; Mattace Raso, G.; Meli, R. Drug targeting of leptin resistance. Life Sci. 2015, 140, 64–74. [Google Scholar] [CrossRef] [PubMed]
- Gao, Y.; Ottaway, N.; Schriever, S.C.; Legutko, B.; García-Cáceres, C.; de la Fuente, E.; Mergen, C.; Bour, S.; Thaler, J.P.; Seeley, R.J.; et al. Hormones and diet, but not body weight, control hypothalamic microglial activity. Glia 2014, 62, 17–25. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frühbeck, G.; Catalán, V.; Rodríguez, A.; Ramírez, B.; Becerril, S.; Portincasa, P.; Gómez-Ambrosi, J. Normalization of adiponectin concentrations by leptin replacement in ob/ob mice is accompanied by reductions in systemic oxidative stress and inflammation. Sci. Rep. 2017, 7, 2752. [Google Scholar] [CrossRef] [PubMed]
- Park, J.H.; Yoo, Y.; Han, J.; Park, Y.J. Altered expression of inflammation-associated genes in the hypothalamus of obesity mouse models. Nutr. Res. 2018. [Google Scholar] [CrossRef]
- Rhea, E.M.; Salameh, T.S.; Logsdon, A.F.; Hanson, A.J.; Erickson, M.A.; Banks, W.A. Blood-brain barriers in obesity. AAPS J. 2017, 19, 921–930. [Google Scholar] [CrossRef] [PubMed]
- Jung, U.J.; Choi, M.S. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci. 2014, 15, 6184–6223. [Google Scholar] [CrossRef] [Green Version]
- Banks, W.A.; Kastin, A.J.; Gutierrez, E.G. Penetration of interleukin-6 across the murine blood-brain barrier. Neurosci. Lett. 1994, 179, 53–56. [Google Scholar] [CrossRef]
- Pan, W.; Kastin, A.J. TNFalpha transport across the blood-brain barrier is abolished in receptor knockout mice. Exp. Neurol. 2002, 174, 193–200. [Google Scholar] [CrossRef]
- Kwak, J.H.; Yang, Z.; Yoon, B.; He, Y.; Uhm, S.; Shin, H.C.; Lee, B.H.; Yoo, Y.C.; Lee, K.B.; Han, S.Y.; et al. Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER stress signaling inhibitors. Biomaterials 2015, 61, 52–60. [Google Scholar] [CrossRef]
© 2019 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
Son, M.; Oh, S.; Choi, J.; Jang, J.T.; Choi, C.H.; Park, K.Y.; Son, K.H.; Byun, K. Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models. Nutrients 2019, 11, 2773. https://doi.org/10.3390/nu11112773
Son M, Oh S, Choi J, Jang JT, Choi CH, Park KY, Son KH, Byun K. Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models. Nutrients. 2019; 11(11):2773. https://doi.org/10.3390/nu11112773
Chicago/Turabian StyleSon, Myeongjoo, Seyeon Oh, Junwon Choi, Ji Tae Jang, Chang Hu Choi, Kook Yang Park, Kuk Hui Son, and Kyunghee Byun. 2019. "Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models" Nutrients 11, no. 11: 2773. https://doi.org/10.3390/nu11112773