Brown Algae Extract Modulates Adipogenesis and Browning in 3T3-L1 Preadipocytes Through HO-1/Nrf2 Signaling

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2024 Aug 28

PMID 39195446

Authors

Indyaswan T Suryaningtyas

Dae-Sung Lee

Jae-Young Je

Affiliations

Soon will be listed here.

Abstract

This study explores the anti-obesity effects of the ethyl acetate extract of (EC-ETAC) on 3T3-L1 preadipocytes, focusing on its impact on adipogenesis, lipolysis, and adipose browning via the HO-1/Nrf2 pathway. Western blot analysis revealed that EC-ETAC significantly inhibited adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1) and lipogenesis-related proteins (FAS, LPL). Concurrently, EC-ETAC enhanced lipolytic markers (p-AMPK, p-HSL) and adipose browning-related proteins (UCP-1, PGC-1α), indicating its role in promoting lipolysis and adipose browning. The inhibition of HO-1 by zinc protoporphyrin (ZnPP) significantly reversed these effects, underscoring the critical role of HO-1 in mediating the anti-obesity properties of EC-ETAC. Additionally, fluorescence measurements and Oil Red O staining confirmed the reduction of lipid accumulation and oxidative stress upon EC-ETAC treatment. These findings suggest that EC-ETAC exerts its anti-obesity effects by modulating the HO-1/Nrf2 pathway, which is crucial for regulating adipogenesis, lipolysis, and adipose browning. This study highlights the potential of EC-ETAC as a natural therapeutic agent for obesity management and supports further research into its clinical applications. By targeting the HO-1/Nrf2 pathway, EC-ETAC could offer a novel approach to enhancing energy expenditure and reducing fat mass, thereby improving metabolic health.

Citing Articles

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References

Vitali A, Murano I, Zingaretti M, Frontini A, Ricquier D, Cinti S . The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res. 2012; 53(4):619-29. PMC: 3307639. DOI: 10.1194/jlr.M018846. View

Lee H, Jayawardena T, Song K, Choi Y, Jeon Y, Kang M . Dietary fucoidan from a brown marine algae (Ecklonia cava) attenuates lipid accumulation in differentiated 3T3-L1 cells and alleviates high-fat diet-induced obesity in mice. Food Chem Toxicol. 2022; 162:112862. DOI: 10.1016/j.fct.2022.112862. View

Kurniawan R, Nurkolis F, Taslim N, Subali D, Surya R, Gunawan W . Carotenoids Composition of Green Algae and Their Antidiabetic, Anti-Obesity, Antioxidant, and Anti-Inflammatory Properties. Molecules. 2023; 28(7). PMC: 10096636. DOI: 10.3390/molecules28073267. View

Choi J, Song N, Lee A, Lee D, Seo M, Kim S . Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice. Int J Mol Sci. 2018; 20(1). PMC: 6337118. DOI: 10.3390/ijms20010026. View

Zhang J, Wu H, Ma S, Jing F, Yu C, Gao L . Transcription regulators and hormones involved in the development of brown fat and white fat browning: transcriptional and hormonal control of brown/beige fat development. Physiol Res. 2018; 67(3):347-362. DOI: 10.33549/physiolres.933650. View

Rayalam S, Yang J, Ambati S, Della-Fera M, Baile C . Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res. 2008; 22(10):1367-71. DOI: 10.1002/ptr.2503. View

Abbas M, Boby N, Lee E, Hong J, Park S . Anti-Obesity Effects of Extract in High-Fat Diet-Induced Obese Rats. Antioxidants (Basel). 2022; 11(2). PMC: 8868354. DOI: 10.3390/antiox11020310. View

Kong X, Banks A, Liu T, Kazak L, Rao R, Cohen P . IRF4 is a key thermogenic transcriptional partner of PGC-1α. Cell. 2014; 158(1):69-83. PMC: 4116691. DOI: 10.1016/j.cell.2014.04.049. View

Wayal V, Hsieh C . Bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet-induced metabolic-associated fatty liver disease via upregulation of Nrf2/HO-1 expressions in C57BL/6J mice. Biomed Pharmacother. 2023; 168:115724. DOI: 10.1016/j.biopha.2023.115724. View

10.

Singh S, Schragenheim J, Cao J, Falck J, Abraham N, Bellner L . PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: Role of epoxyeicosatrienoic acid. Prostaglandins Other Lipid Mediat. 2016; 125:8-18. PMC: 5536246. DOI: 10.1016/j.prostaglandins.2016.07.004. View

11.

Choi H, Jeon H, Lee O, Lee B . Dieckol, a major phlorotannin in Ecklonia cava, suppresses lipid accumulation in the adipocytes of high-fat diet-fed zebrafish and mice: Inhibition of early adipogenesis via cell-cycle arrest and AMPKα activation. Mol Nutr Food Res. 2015; 59(8):1458-71. DOI: 10.1002/mnfr.201500021. View

12.

Liang G, Fang J, Zhang P, Ding S, Zhao Y, Feng Y . Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity. Open Med (Wars). 2024; 19(1):20240900. PMC: 10921440. DOI: 10.1515/med-2024-0900. View

13.

Kang C, Jin Y, Lee H, Cha M, Sohn E, Moon J . Brown alga Ecklonia cava attenuates type 1 diabetes by activating AMPK and Akt signaling pathways. Food Chem Toxicol. 2009; 48(2):509-16. DOI: 10.1016/j.fct.2009.11.004. View

14.

Lamichane S, Dahal Lamichane B, Kwon S . Pivotal Roles of Peroxisome Proliferator-Activated Receptors (PPARs) and Their Signal Cascade for Cellular and Whole-Body Energy Homeostasis. Int J Mol Sci. 2018; 19(4). PMC: 5979443. DOI: 10.3390/ijms19040949. View

15.

Man A, Zhou Y, Xia N, Li H . Perivascular Adipose Tissue as a Target for Antioxidant Therapy for Cardiovascular Complications. Antioxidants (Basel). 2020; 9(7). PMC: 7402161. DOI: 10.3390/antiox9070574. View

16.

Chen L, Liu R, He X, Pei S, Li D . Effects of brown seaweed polyphenols, a class of phlorotannins, on metabolic disorders via regulation of fat function. Food Funct. 2021; 12(6):2378-2388. DOI: 10.1039/d0fo02886j. View

17.

Park E, Kim E, Kim M, Seo Y, Lee J, Jun H . Polyphenol-Rich Fraction of Brown Alga Ecklonia cava Collected from Gijang, Korea, Reduces Obesity and Glucose Levels in High-Fat Diet-Induced Obese Mice. Evid Based Complement Alternat Med. 2012; 2012:418912. PMC: 3403644. DOI: 10.1155/2012/418912. View

18.

Zhang A, Suzuki T, Adachi S, Naganuma E, Suzuki N, Hosoya T . Distinct Regulations of Gene Expression for Stress Response and Substrate Induction. Mol Cell Biol. 2021; 41(11):e0023621. PMC: 8547446. DOI: 10.1128/MCB.00236-21. View

19.

Son M, Oh S, Lee H, Ryu B, Jiang Y, Jang J . Pyrogallol-Phloroglucinol-6,6'-Bieckol from Improved Blood Circulation in Diet-Induced Obese and Diet-Induced Hypertension Mouse Models. Mar Drugs. 2019; 17(5). PMC: 6562948. DOI: 10.3390/md17050272. View

20.

Choi H, Jeon E, Kim D, Choi M, Yu H, Kim J . Sodium salicylate induces browning of white adipocytes via M2 macrophage polarization by HO-1 upregulation. Eur J Pharmacol. 2022; 928:175085. DOI: 10.1016/j.ejphar.2022.175085. View