Anti-Obesity Activity of the Marine Carotenoid Fucoxanthin
<p>The chemical structure of fucoxanthin.</p> "> Figure 2
<p>The metabolic conversion of fucoxanthin to amarouciaxanthin A via fucoxanthinol.</p> "> Figure 3
<p>Effects of fucoxanthin on weight loss and lipid metabolism, compared to insulin: fucoxanthin significantly reduces plasmatic and hepatic triglyceride concentrations and cholesterol uptake in the liver via down-regulation of Low-Density Lipoprotein (LDL)-receptor and Scavenger receptor class B member 1 (SR-B1). Fucoxanthin supplementation also decreased mRNA expression of fatty acid synthase (FAS), which catalyzes fatty acid synthesis. It also inhibited the uptake of glucose in mature adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). Fucoxanthin significantly reduced plasmatic and hepatic triglyceride concentrations and positively influenced cholesterol-regulating enzymes activities such as 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA and affects gene expression associated with lipid metabolism: in rats its supplementation decreased mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA.</p> "> Figure 4
<p>Effects of fucoxanthin on thermogenesis and lipolysis: the muscle (<b>a</b>) and the adipose tissue (<b>b</b>). Fucoxanthin plays an anti-obesity effect mainly by stimulating uncoupling protein-1 (UCP-1) expression in white adipose tissue (WAT). This protein, situated in the mitochondrial inner cellular membrane, is usually found in brown adipose tissue (BAT) and it is not expressed in WAT in absence of any stimulation. Physiologic bodily metabolism determines heat production: this process is named thermogenesis and UCP-1 dissipates the pH-gradient generated by oxidative phosphorylation, releasing chemical energy as heat. Fucoxanthin was found to promote not only UCP1 protein and mRNA expression but also β3-adrenergic receptor (Adrb3), which is responsible for lipolysis and thermogenesis. This increased sensitivity to sympathetic nerve stimulation may lead to a further up-regulation of fat oxidation in WAT. This adaptive thermogenesis plays a crucial role in energy expenditure as heat, in order to limit weight gain and to favor weight loss.</p> "> Figure 5
<p>Effects of fucoxanthin on glucidic and lipid metabolism: from the enterocyte to the hepatocyte. Fucoxanthin increases fatty acids oxidation and decreases the hepatic lipid contents by regulating metabolic enzyme activities and stimulating β-oxidation activity. Hepatic lipid contents resulted to be markedly lower after fucoxanthin supplementation because fucoxanthin inhibits hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase and phosphatidate phosphohydrolase, which are involved in the hepatic lipid droplet. In addition, an important effect of fucoxanthin in enterocytes, such as competition with lipid absorption can be postulated.</p> ">
Abstract
:1. Introduction
2. Structure and Metabolism of Fucoxanthin
3. Anti-Obesity Effect
3.1. Fucoxanthin and Uncoupling Proteins: Adaptive Thermogenesis as a Physiological Defense against Obesity
3.2. Fucoxanthin and Leptin Regulation
4. Obesity and Non Alcoholic Fat Liver Disease: Hepatoprotective Effect of Fucoxanthin
5. Obesity and Oxidative Stress: Antioxidant and Anti-Inflammatory Effects of Fucoxanthin
6. Genetic and Iatrogenic Aspects of Obesity: The Potential of Fucoxanthin
7. Conclusions
Author Contributions
Conflicts of Interest
References
- Kuipers, R.S.; de Graaf, D.J.; Luxwolda, M.F.; Muskiet, M.H.; Dijck-Brouwer, D.A.; Muskiet, F.A. Saturated fat, carbohydrates and cardiovascular disease. Neth. J. Med. 2011, 69, 372–378. [Google Scholar] [PubMed]
- Kim, S.M.; Jung, Y.H.; Kwon, O.; Cha, K.H.; Um, B.H. A potential commercial source of fucoxanthin extracted from the microalga Phaeodactylum tricornutum. Appl. Biochem. Biotechnol. 2012, 166, 1843–1855. [Google Scholar] [CrossRef] [PubMed]
- Maeda, H.; Hosokawa, M.; Sashima, T.; Miyashita, K. Dietary combination of fucoxanthin and fish oil attenuates the weight gain of white adipose tissue and decreases blood glucose in obese/diabetic KK-Ay mice. J. Agric. Food Chem. 2007, 55, 7701–7706. [Google Scholar] [CrossRef] [PubMed]
- Woo, M.N.; Jeon, S.M.; Kim, H.J.; Lee, M.K.; Shin, S.K.; Shin, Y.C.; Park, Y.B.; Choi, M.S. Fucoxanthin supplementation improves plasma and hepatic lipid metabolism and blood glucose concentration in high-fat fed C57BL/6N mice. Chem. Biol. Interact. 2010, 186, 316–322. [Google Scholar] [CrossRef] [PubMed]
- Sangeetha, R.K.; Bhaskar, N.; Baskaran, V. Comparative effects of β-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats. Mol. Cell. Biochem. 2009, 331, 59–67. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.J.; Bai, S.K.; Lee, K.S.; Namkoong, S.; Na, H.J.; Ha, K.S.; Han, J.A.; Yim, S.V.; Chang, K.; Kwon, Y.G.; et al. Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(κ)B kinase-dependent NF-κB activation. Mol. Cells 2003, 16, 97–105. [Google Scholar] [PubMed]
- Kim, K.N.; Ahn, G.; Heo, S.J.; Kang, S.M.; Kang, M.C.; Yang, H.M.; Kim, D.; Roh, S.W.; Kim, S.K.; Jeon, B.T.; et al. Inhibition of tumor growth in vitro and in vivo by fucoxanthin against melanoma B16-F10 cells. Envir. Toxicol. Pharmacol. 2013, 35, 39–46. [Google Scholar] [CrossRef]
- McNulty, H.; Jacob, R.F.; Mason, R.P. Biologic activity of carotenoids related to distinct membrane physicochemical interactions. Am. J. Cardiol. 2008, 101, 20D–29D. [Google Scholar] [CrossRef] [PubMed]
- Seifried, H.E.; Anderson, D.E.; Fisher, E.I.; Milner, J.A. A review of the interaction among dietary antioxidants and reactive oxygen species. J. Nutr. Biochem. 2007, 18, 567–579. [Google Scholar] [CrossRef] [PubMed]
- Hu, T.; Liu, D.; Chen, Y.; Wu, J.; Wang, S. Antioxidant activity of sulfated polysaccharide fractions extracted from Undaria pinnitafida in vitro. Int. J. Biol. Macromol. 2010, 46, 193–198. [Google Scholar] [CrossRef] [PubMed]
- Sangeetha, R.K.; Bhaskar, N.; Divakar, S.; Baskaran, V. Bioavailability and metabolism of fucoxanthin in rats: Structural characterization of metabolites by LC–MS (APCI). Mol. Cell. Biochem. 2010, 333, 299–310. [Google Scholar] [CrossRef] [PubMed]
- Das, S.K.; Hashimoto, T.; Kanazawa, K. Growth inhibition of human hepatic carcinoma Hep-G2 cells by fucoxanthin is associated with down-regulation of cyclin D. Biochim. Biophys. Acta 2008, 1780, 743–749. [Google Scholar] [CrossRef] [PubMed]
- Asai, A.; Sugawara, T.; Ono, H.; Nagao, A. Biotransformation of fucoxanthinol in amarouciaxanthin A in mice and Hep-G2 cells: Formation and cytotoxicity of fucoxanthin metabolites. Drug Metab. Dispos. 2004, 32, 205–211. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, T.; Ozaki, Y.; Taminato, M.; Das, S.K.; Mizuno, M.; Yoshimura, K.; Maoka, T.; Kanazawa, K. The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br. J. Nutr. 2009, 102, 242–248. [Google Scholar] [CrossRef] [PubMed]
- Gammone, M.A.; Riccioni, G.; D’Orazio, N. Carotenoids: Potential allies of cardiovascular health? Food Nutr. Res. 2015, 59, 26762. [Google Scholar] [CrossRef] [PubMed]
- Asai, A.; Yonekura, L.; Nagao, A. Low bioavailability of dietary epoxy-xanthophylls in humans. Br. J. Nutr. 2008, 100, 273–277. [Google Scholar] [CrossRef] [PubMed]
- Hu, X.; Li, Y.; Li, C.; Fu, Y.; Cai, F.; Chen, Q.; Li, D. Combination of fucoxanthin and conjugated linoleic acid attenuates body weight gain and improves lipid metabolism in high-fat diet-induced obese rats. Arch. Biochem. Biophys. 2012, 519, 59–65. [Google Scholar] [CrossRef] [PubMed]
- Tong, L. Acetyl-coenzyme A carboxylase: Crucial metabolic enzyme and attractive target for drug discovery. Cell. Mol. Life Sci. 2005, 62, 1784–1803. [Google Scholar] [CrossRef] [PubMed]
- Beppu, F.; Hosokawa, M.; Niwano, Y.; Miyashita, K. Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A(y) mice. Lipids Health Dis. 2012, 11, 112. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.; Singh, S.B.; Wang, J.; Chung, C.C.; Salituro, G.; Karanam, B.V.; Lee, S.H.; Powles, M.; Ellsworth, K.P.; Lassman, M.E.; et al. Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes. Proc. Natl. Acad. Sci. USA 2011, 108, 5378–5383. [Google Scholar] [CrossRef] [PubMed]
- Beppu, F.; Hosokawa, M.; Yim, M.J.; Shinoda, T.; Miyashita, K. Down-regulation of hepatic stearoyl-CoA desaturase-1 expression by fucoxanthin via leptin signaling in diabetic/obese KK-A(y) mice. Lipids 2013, 48, 449–455. [Google Scholar] [CrossRef] [PubMed]
- Aster, J.; Kumar, V.; Robbins, S.L.; Abbas, A.K.; Fausto, N.; Cotran, R.S. Robbins and Cotran Pathologic Basis of Disease, 8th ed.; Saunders/Elsevier: Philadelphia, PA, USA, 2010; Volume 33, pp. 340–341. [Google Scholar]
- Eberlé, D.; Hegarty, B.; Bossard, P.; Ferré, P.; Foufelle, F. SREBP transcription factors: Master regulators of lipid homeostasis. Biochimie 2004, 86, 839–848. [Google Scholar] [CrossRef] [PubMed]
- Ferré, P.; Foufelle, F. Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes. Metab. 2010, 12, 83–92. [Google Scholar] [CrossRef] [PubMed]
- DeVries, R.; Borggreve, S.E.; Dullaart, R.P. Role of lipases, lecithin: Cholesterol acyltransferase and cholesteryl ester transfer protein in abnormal high density lipoprotein metabolism in insulin resistance and type 2 diabetes mellitus. Clin. Lab. 2004, 49, 601–613. [Google Scholar]
- Rasmussen, B.B.; Holmbäck, U.C.; Volpi, E.; Morio-Liondore, B.; Paddon-Jones, D.; Wolfe, R.R. Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle. J. Clin. Invest. 2002, 110, 1687–1693. [Google Scholar] [CrossRef] [PubMed]
- Maeda, H.; Hosokawa, M.; Sashima, T.; Murakami-Funayama, K.; Miyashita, K. Anti-obesity and anti-diabetic effects of fucoxanthin on diet-induced obesity conditionsin a murine model. Mol. Med. Rep. 2009, 2, 897–902. [Google Scholar] [CrossRef] [PubMed]
- Kang, S.I.; Shin, H.S.; Kim, H.M.; Yoon, S.A.; Kang, S.W.; Kim, J.H.; Ko, H.C.; Kim, S.J. Petalonia binghamiae extract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinase. J. Agric. Food Chem. 2012, 60, 3389–3395. [Google Scholar] [CrossRef] [PubMed]
- Ntambi, J.M.; Kim, Y.C. Adipocyte differentiation and gene expression. J. Nutr. 2000, 12, 3122–3126. [Google Scholar]
- Kang, S.I.; Ko, H.C.; Shin, H.S.; Kim, H.M.; Hong, Y.S.; Lee, N.H.; Kim, S.J. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes. Biochem. Biophys. Res. Commun. 2011, 409, 769–777. [Google Scholar] [CrossRef] [PubMed]
- Maeda, H.; Hosokawa, M.; Sashima, T.; Takahashi, N.; Kawada, T.; Miyashita, K. Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Intern. J. Mol. Med. 2006, 18, 147–152. [Google Scholar]
- Yim, M.J.; Hosokawa, M.; Mizushina, Y.; Yoshida, H.; Saito, Y.; Miyashita, K. Suppressive effects of amarouciaxanthin A on 3T3-L1 adipocyte differentiation through down-regulation of PPAR-γ and C/EBPr mRNA expression. J. Agric. Food Chem. 2011, 59, 1646–1652. [Google Scholar] [CrossRef] [PubMed]
- D’Orazio, N.; Gemello, E.; Gammone, M.A.; DeGirolamo, M.; Ficoneri, C.; Riccioni, G. Fucoxantin: A treasure from the sea. Mar. Drugs 2012, 10, 604–616. [Google Scholar] [CrossRef] [PubMed]
- Gammone, M.A.; Gemello, E.; Riccioni, G.; D’Orazio, N. Marine bioactives and potential application in sports. Mar. Drugs 2014, 12, 2357–2382. [Google Scholar] [CrossRef] [PubMed]
- Maeda, H.; Hosokawa, M.; Sashima, T.; Funayama, K.; Miyashita, K. Fucoxanthin from edible seaweed Undaria pinnatifida, shows anti-obesity effect through UCP1 expression in white adipose tissues. Biochem. Biophys. Res. Commun. 2005, 332, 392–397. [Google Scholar] [CrossRef] [PubMed]
- Abidov, M.; Ramazanov, Z.; Seifulla, R.; Grachev, S. The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat. Diabet. Obes. Metable 2010, 12, 72–81. [Google Scholar] [CrossRef]
- Heilbronn, L.K.; Noakes, M.; Clifton, M.P. Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women. Atheroscler. Thromb. Vasc. Biol. 2001, 21, 968–970. [Google Scholar] [CrossRef]
- Hosokawa, M.; Miyashita, T.; Nishikawa, S.; Emi, S.; Tsukui, T.; Beppu, F.; Okada, T.; Miyashita, K. Fucoxanthin regulates adipocytokine mRNA expression in white adipose tissue of diabetic/obese KK-Ay mice. Arch. Biochem. Biophys. 2010, 504, 17–25. [Google Scholar] [CrossRef] [PubMed]
- Gautron, L.; Elmquist, J.K. Sixteen years and counting: An update on leptin in energy balance. J. Clin. Invest. 2011, 121, 2087–2093. [Google Scholar] [CrossRef] [PubMed]
- Roujeau, C.; Jockers, R.; Dam, J. New pharmacological perspectives for the leptin receptor in the treatment of obesity. Front Endocrinol. 2014, 13, 5–167. [Google Scholar]
- Park, H.J.; Lee, M.K.; Park, Y.B.; Shin, Y.C.; Choi, M.S. Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice. Food Chem. Toxicol. 2011, 49, 727–733. [Google Scholar] [CrossRef] [PubMed]
- Tsujino, N.; Sakurai, T. Circadian rhythm of leptin, orexin and ghrelin. Nihon Rinsho 2012, 70, 1121–1125. [Google Scholar] [PubMed]
- Sakurai, T. Roles of orexins and orexin receptors in central regulation of feeding behavior and energy homeostasis. CNS Neurol. Disord. Drug Targets 2006, 5, 313–325. [Google Scholar] [CrossRef] [PubMed]
- Blundell, J.E.; Gibbons, C.; Caudwell, P.; Finlayson, G.; Hopkins, M. Appetite control and energy balance: Impact of exercise. Obes. Rev. 2015, 16, 67–76. [Google Scholar] [CrossRef] [PubMed]
- Maeda, H.; Tsukui, T.; Sashima, T.; Hosokawa, M.; Miyashita, K. Seaweed carotenoid, fucoxanthin, as a multi-functional nutrient. Asia Pac. J. Clin. Nutr. 2008, 17, 196–199. [Google Scholar] [PubMed]
- Tsukui, T.; Konno, K.; Hosokawa, M.; Maeda, H.; Sashima, T.; Miyashita, K. Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the liver of KKAy obese/diabetic mice. J. Agric. Food Chem. 2007, 55, 5025–5029. [Google Scholar] [CrossRef] [PubMed]
- Tsukui, T.; Baba, T.; Hosokawa, M.; Sashima, T.; Miyashita, K. Enhancement of hepatic docosahexaenoic acid and arachidonic acid contents in C57BL/6J mice by dietary fucoxanthin. Fish. Sci. 2009, 75, 261–263. [Google Scholar] [CrossRef]
- Airanthi, M.K.W.A.; Sasaki, N.; Iwasaki, S.; Baba, N.; Abe, M.; Hosokawa, M.; Miyashita, K. Effect of brown seaweed lipids on fatty acid composition and lipid hydroperoxide levels of mouse liver. J. Agric. Food Chem. 2011, 59, 4156–4163. [Google Scholar] [CrossRef] [PubMed]
- Masterton, G.S.; Plevris, J.N.; Hayes, P.C. Review article: Omega-3 fatty acids–A promising novel therapy for non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2010, 31, 679–692. [Google Scholar] [CrossRef] [PubMed]
- Dandona, P.; Aljada, A.; Chaudhuri, A.; Mohanty, P.; Garg, R. Metabolic syndrome: A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005, 111, 1448–1454. [Google Scholar] [CrossRef] [PubMed]
- D’Orazio, N.; Gammone, M.A.; Gemello, E.; DeGirolamo, M.; Cusenza, S.; Riccioni, G. Marine bioactives: Pharmacological properties and potential applications against inflammatory diseases. Mar. Drugs 2012, 10, 812–833. [Google Scholar] [CrossRef] [PubMed]
- Ha, A.W.; Na, S.J.; Kim, W.K. Antioxidant effects of fucoxanthin rich powder in rats fed with high fat diet. Nutr. Res. Pract. 2013, 7, 475–480. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.L.; Chiu, Y.T.; Hu, M.L. Fucoxanthin enhances HO-1 and NQO1 expression in murine hepatic BNL CL.2 cells through activation of the Nrf2/ARE system partially by its pro-oxidant activity. J. Agric. Food Chem. 2011, 59, 11344–11351. [Google Scholar] [CrossRef] [PubMed]
- Orton, R.J.; Sturm, O.E.; Vyshemirsky, V.; Calder, M.; Gilbert, D.R.; Kolch, W. Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem. J. 2005, 392, 249–261. [Google Scholar] [CrossRef] [PubMed]
- Kim, K.N.; Heo, S.J.; Kang, S.M.; Ahn, G.; Jeon, Y.J. Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway. Toxicol. Vitro 2010, 24, 1648–1654. [Google Scholar] [CrossRef]
- Kim, K.N.; Heo, S.J.; Yoon, W.J.; Kang, S.M.; Ahn, G.; Yi, T.H.; Jeon, Y.J. Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-κB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur. J. Pharmacol. 2010, 649, 369–375. [Google Scholar] [CrossRef] [PubMed]
- Sakai, S.; Sugawara, T.; Matsubara, K.; Hirata, T. Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptor. J. Biol. Chem. 2009, 284, 28172–28179. [Google Scholar] [CrossRef] [PubMed]
- Brondani, L.A.; Assmann, T.S.; Duarte, G.C.; Gross, J.L.; Canani, L.H.; Crispim, D. The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus. Arq Bras. Endocrinol. Metabol. 2012, 56, 215–225. [Google Scholar] [CrossRef] [PubMed]
- Jia, J.J.; Tian, Y.B.; Cao, Z.H.; Tao, L.L.; Zhang, X.; Gao, S.Z. The polymorphisms of UCP1 genes associated with fat metabolism, obesity and diabetes. Mol. Biol. Rep. 2010, 37, 1513–1522. [Google Scholar] [CrossRef] [PubMed]
- Clément, K.; Ruiz, J.; Cassard-Doulcier, A.M.; Bouillaud, F.; Ricquier, D.; Basdevant, A.; Guy-Grand, B.; Froguel, P. Additive effect of A→G (-3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the β3-adrenergic receptor gene on weight gain in morbid obesity. Int. J. Obes. Relat. Metab. Disord. 1996, 20, 1062–1066. [Google Scholar] [PubMed]
- Fogelholm, M.; Valve, R.; Kukkonen-Harjula, K.; Nenonen, A.; Hakkarainen, V.; Laakso, M. Additive effects of the mutations in the β3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women. J. Clin. Endocrinol. Metab. 1998, 83, 4246–4250. [Google Scholar] [PubMed]
- Schäffler, A.; Palitzsch, K.D.; Watzlawek, E.; Drobnik, W.; Schwer, H.; Schölmerich, J. Frequency and significance of the A→G (-3826) polymorphism in the promoter of the gene for uncoupling protein-1 with regard to metabolic parameters and adipocyte transcription factor binding in a large population-based Caucasian cohort. Eur. J. Clin. Invest. 1999, 29, 770–779. [Google Scholar] [CrossRef] [PubMed]
- Lu, M.; Wang, T.; Lin, T.; Shao, W.; Chang, S.; Chou, J.; Ho, Y.; Liao, Y.; Chen, V.C. Differential effects of olanzapine and clozapine on plasma levels of adipocytokines and total ghrelin. Prog. Neuropsychopharmacol. Biol. Psychiatry 2014, 9, 47–50. [Google Scholar]
- Domecq, J.P.; Prutsky, G.; Leppin, A.; Sonbol, M.B.; Altayar, O.; Undavalli, C.; Wang, Z.; Elraiyah, T.; Brito, J.P.; Mauck, K.F.; et al. Drugs commonly associated with weight change: A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2015, 15, 1–8. [Google Scholar]
- Lamp, Y.; Eshel, Y.; Rapaport, A.; Sarova-Pinhas, I. Weight gain, increased appetite, and excessive food intake induced by carbamazepine. Clin. Neuropharmacol. 1991, 14, 251–255. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Obin, M.S.; Zhao, L. The gut microbiota, obesity and insulin resistance. Mol. Aspects Med. 2013, 34, 39–58. [Google Scholar] [CrossRef] [PubMed]
- Stachowicz, N.; Kiersztan, A. The role of gut microbiota in the pathogenesis of obesity and diabetes. Postepy Hig. Med. Dosw. 2013, 67, 288–303. [Google Scholar] [CrossRef]
© 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gammone, M.A.; D'Orazio, N. Anti-Obesity Activity of the Marine Carotenoid Fucoxanthin. Mar. Drugs 2015, 13, 2196-2214. https://doi.org/10.3390/md13042196
Gammone MA, D'Orazio N. Anti-Obesity Activity of the Marine Carotenoid Fucoxanthin. Marine Drugs. 2015; 13(4):2196-2214. https://doi.org/10.3390/md13042196
Chicago/Turabian StyleGammone, Maria Alessandra, and Nicolantonio D'Orazio. 2015. "Anti-Obesity Activity of the Marine Carotenoid Fucoxanthin" Marine Drugs 13, no. 4: 2196-2214. https://doi.org/10.3390/md13042196