Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD Through Modulation of Leptin/Adiponectin Axis

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2021 Apr 3

PMID 33809062

Citations 30

Authors

Ping-Hsiao Shih

Sheng-Jie Shiue

Chun-Nan Chen

Sheng-Wei Cheng

Hsin-Yi Lin

Li-Wei Wu

Ming-Shun Wu

Affiliations

Soon will be listed here.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

Citing Articles

Fucoidan ameliorates lipid accumulation, oxidative stress, and NF-κB-mediated inflammation by regulating the PI3K/AKT/Nrf2 signaling pathway in a free fatty acid-induced NAFLD spheroid model.

Chu X, Wang X, Feng K, Bi Y, Xin Y, Liu S Lipids Health Dis. 2025; 24(1):55.

PMID: 39962463 PMC: 11831825. DOI: 10.1186/s12944-025-02483-z.

Evaluating Bioactive-Substance-Based Interventions for Adults with MASLD: Results from a Systematic Scoping Review.

Handu D, Stote K, Piemonte T Nutrients. 2025; 17(3).

PMID: 39940310 PMC: 11820841. DOI: 10.3390/nu17030453.

Marine Algae and Deriving Biomolecules for the Management of Inflammatory Bowel Diseases: Potential Clinical Therapeutics to Decrease Gut Inflammatory and Oxidative Stress Markers?.

Repici A, Hasan A, Capra A, Scuderi S, Paterniti I, Campolo M Mar Drugs. 2024; 22(8).

PMID: 39195452 PMC: 11355360. DOI: 10.3390/md22080336.

The Effect of and on Continuous Glucose Levels in Overweight Patients with Type 2 Diabetes Mellitus: A Feasibility Randomized, Double-Blind, Placebo-Controlled Trial.

Geurts K, Meijer S, Roeters van Lennep J, Wang X, Ozcan B, Voortman G Nutrients. 2024; 16(12).

PMID: 38931192 PMC: 11206271. DOI: 10.3390/nu16121837.

Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis.

Xu Y, Xue M, Li J, Ma Y, Wang Y, Zhang H Nutrients. 2024; 16(10).

PMID: 38794753 PMC: 11124141. DOI: 10.3390/nu16101512.

References

Fruhbeck G, Catalan V, Rodriguez A, Ramirez B, Becerril S, Salvador J . Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome. Sci Rep. 2017; 7(1):6619. PMC: 5529549. DOI: 10.1038/s41598-017-06997-0. View

Breda E, Cavaghan M, Toffolo G, Polonsky K, Cobelli C . Oral glucose tolerance test minimal model indexes of beta-cell function and insulin sensitivity. Diabetes. 2001; 50(1):150-8. DOI: 10.2337/diabetes.50.1.150. View

Lin H, Tsou Y, Chen Y, Lu W, Hwang P . Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes. Mar Drugs. 2017; 15(4). PMC: 5408259. DOI: 10.3390/md15040113. View

Sonoda J, Laganiere J, Mehl I, Barish G, Chong L, Li X . Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev. 2007; 21(15):1909-20. PMC: 1935029. DOI: 10.1101/gad.1553007. View

Hashimoto T, Ozaki Y, Taminato M, Das S, Mizuno M, Yoshimura K . The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice. Br J Nutr. 2009; 102(2):242-8. DOI: 10.1017/S0007114508199007. View

Lin J, Yang R, Tarr P, Wu P, Handschin C, Li S . Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell. 2005; 120(2):261-73. DOI: 10.1016/j.cell.2004.11.043. View

Haas J, Francque S, Staels B . Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease. Annu Rev Physiol. 2015; 78:181-205. DOI: 10.1146/annurev-physiol-021115-105331. View

Khan S, Sathyanarayan A, Mashek M, Ong K, Wollaston-Hayden E, Mashek D . ATGL-catalyzed lipolysis regulates SIRT1 to control PGC-1α/PPAR-α signaling. Diabetes. 2015; 64(2):418-26. PMC: 4303962. DOI: 10.2337/db14-0325. View

Muradian K, Vaiserman A, Min K, Fraifeld V . Fucoxanthin and lipid metabolism: A minireview. Nutr Metab Cardiovasc Dis. 2015; 25(10):891-7. DOI: 10.1016/j.numecd.2015.05.010. View

10.

Pierantonelli I, Svegliati-Baroni G . Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH. Transplantation. 2018; 103(1):e1-e13. DOI: 10.1097/TP.0000000000002480. View

11.

Hwang P, Phan N, Lu W, Ngoc Hieu B, Lin Y . Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells. Food Nutr Res. 2016; 60:32033. PMC: 4973444. DOI: 10.3402/fnr.v60.32033. View

12.

Reeves P, Nielsen F, Fahey Jr G . AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993; 123(11):1939-51. DOI: 10.1093/jn/123.11.1939. View

13.

Heeba G, Morsy M . Fucoidan ameliorates steatohepatitis and insulin resistance by suppressing oxidative stress and inflammatory cytokines in experimental non-alcoholic fatty liver disease. Environ Toxicol Pharmacol. 2015; 40(3):907-14. DOI: 10.1016/j.etap.2015.10.003. View

14.

Luthuli S, Wu S, Cheng Y, Zheng X, Wu M, Tong H . Therapeutic Effects of Fucoidan: A Review on Recent Studies. Mar Drugs. 2019; 17(9). PMC: 6780838. DOI: 10.3390/md17090487. View

15.

Ji Y, Yin Y, Li Z, Zhang W . Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients. 2019; 11(8). PMC: 6724003. DOI: 10.3390/nu11081712. View

16.

Zheng Y, Liu T, Wang Z, Xu Y, Zhang Q, Luo D . Low molecular weight fucoidan attenuates liver injury via SIRT1/AMPK/PGC1α axis in db/db mice. Int J Biol Macromol. 2018; 112:929-936. DOI: 10.1016/j.ijbiomac.2018.02.072. View

17.

Shiue S, Rau R, Shiue H, Hung Y, Li Z, Yang K . Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats. Pain. 2018; 160(1):210-223. DOI: 10.1097/j.pain.0000000000001395. View

18.

Vaamonde-Garcia C, Florez-Fernandez N, Torres M, Lamas-Vazquez M, Blanco F, Dominguez H . Study of fucoidans as natural biomolecules for therapeutical applications in osteoarthritis. Carbohydr Polym. 2021; 258:117692. DOI: 10.1016/j.carbpol.2021.117692. View

19.

Hayashi S, Itoh A, Isoda K, Kondoh M, Kawase M, Yagi K . Fucoidan partly prevents CCl4-induced liver fibrosis. Eur J Pharmacol. 2007; 580(3):380-4. PMC: 2258315. DOI: 10.1016/j.ejphar.2007.11.015. View

20.

Araujo A, Rosso N, Bedogni G, Tiribelli C, Bellentani S . Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: What we need in the future. Liver Int. 2018; 38 Suppl 1:47-51. DOI: 10.1111/liv.13643. View