10‑Gingerol, a novel ginger compound, exhibits antiadipogenic effects without compromising cell viability in 3T3‑L1 cells

Preciado‑Ortiz,María Elizabeth; Martinez‑Lopez,Erika; Rodriguez‑Echevarría,Roberto; Perez‑Robles,Mariana; Gembe‑Olivarez,Gildardo; Rivera‑Valdés,Juan José

doi:10.3892/br.2023.1687

10‑Gingerol, a novel ginger compound, exhibits antiadipogenic effects without compromising cell viability in 3T3‑L1 cells

Authors:
- María Elizabeth Preciado‑Ortiz
- Erika Martinez‑Lopez
- Roberto Rodriguez‑Echevarría
- Mariana Perez‑Robles
- Gildardo Gembe‑Olivarez
- Juan José Rivera‑Valdés
View Affiliations

Affiliations: Institute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular Biology and Genomics, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico
Published online on: November 1, 2023 https://doi.org/10.3892/br.2023.1687
Article Number: 105
Copyright: © Preciado‑Ortiz et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Obesity is defined as excessive fat accumulation that can be detrimental to health and currently affects a large part of the global population. Obesity arises from excessive energy intake along with a sedentary lifestyle and leads to adipocytes with aggravated hypertrophy. Strategies have been designed to prevent and treat obesity. Nutrigenomics may serve a role in prevention of obesity using bioactive compounds present in certain foods with anti‑obesogenic effects. Ginger (Zingiber officinale Roscoe) contains gingerols, key bioactive compounds that inhibit hypertrophy and hyperplasia of adipocytes. The present study aimed to evaluate the antiadipogenic activity of 10‑gingerol (10‑G) in the 3T3‑L1 cell line. Three study groups were formed: Negative (3T3‑L1 preadipocytes) and positive control (mature 3T3‑L1 adipocytes) and 10‑G (3T3‑L1 preadipocytes stimulated with 10‑G during adipogenic differentiation). Cell viability and lipid content were evaluated by MTT assay and Oil Red O staining, respectively. mRNA expression of CCAAT enhancer‑binding protein α (C/ebpα), peroxisome proliferator‑activated receptor γ (Pparγ), mechanistic target of rapamycin complex (Mtor), sterol regulatory element binding transcription factor 1 (Srebf1), acetyl‑coenzyme A carboxylase (Acaca), fatty acid binding protein 4 (Fabp4), and 18S rRNA (Rn18s), was quantified by quantitative PCR. The protein expression of C/EPBα was analyzed by western blot. In the 10‑G group, lipid content was decreased by 28.83% (P<0.0001) compared with the positive control; notably, cell viability was not affected (P=0.336). The mRNA expression in the 10‑G group was higher for C/ebpα (P<0.001) and lower for Acaca (P<0.001), Fabp4 (P<0.001), Mtor (P<0.0001) and Srebf1 (P<0.0001) compared with the positive control group, while gene expression of Pparγ did not present significant changes. The presence of 10‑G notably decreased C/EBPα protein levels in 3T3‑L1 adipocytes. In summary, the antiadipogenic effect of 10‑G during the differentiation of 3T3‑L1 cells into adipocytes may be explained by mRNA downregulation of adipogenic transcriptional factors and lipid metabolism‑associated genes.

View Figures

View References

1	González-Muniesa P, Mártinez-González MA, Hu FB, Després JP, Matsuzawa Y, Loos RJF, Moreno LA, Bray GA and Martinez JA: Obesity. Nat Rev Dis Prim. 3(17034)2017.PubMed/NCBI View Article : Google Scholar
2	Blüher M: Obesity: Global epidemiology and pathogenesis. Nat Rev Endocrinol. 15:288–298. 2019.PubMed/NCBI View Article : Google Scholar
3	World Health Organization (WHO): Obesity and overweight. WHO, Geneva, 2021.
4	Heymsfield SB and Wadden TA: Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 376:254–266. 2017.PubMed/NCBI View Article : Google Scholar
5	Doo M and Kim Y: . Obesity: Interactions of genome and nutrients intake. Prev Nutr Food Sci. 20:1–7. 2015.PubMed/NCBI View Article : Google Scholar
6	Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T and Li HB: Bioactive compounds and bioactivities of ginger (zingiber officinale roscoe). Foods. 8(185)2019.PubMed/NCBI View Article : Google Scholar
7	Wang J, Ke W, Bao R, Hu X and Chen F: Beneficial effects of ginger Zingiber officinale Roscoe on obesity and metabolic syndrome: A review. Ann N Y Acad Sci. 1398:83–98. 2017.PubMed/NCBI View Article : Google Scholar
8	Saravanan G, Ponmurugan P, Deepa MA and Senthilkumar B: Anti-obesity action of gingerol: Effect on lipid profile, insulin, leptin, amylase and lipase in male obese rats induced by a high-fat diet. J Sci Food Agric. 94:2972–2977. 2014.PubMed/NCBI View Article : Google Scholar
9	Semwal RB, Semwal DK, Combrinck S and Viljoen AM: Gingerols and shogaols: Important nutraceutical principles from ginger. Phytochemistry. 117:554–568. 2015.PubMed/NCBI View Article : Google Scholar
10	Tzeng TF and Liu IM: 6-Gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells. Phytomedicine. 20:481–487. 2013.PubMed/NCBI View Article : Google Scholar
11	Li C and Zhou L: Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes. Toxicol In Vitro. 30 (1 Pt B):394–401. 2015.PubMed/NCBI View Article : Google Scholar
12	Rani MP, Krishna MS, Padmakumari KP, Raghu KG and Sundaresan A: Zingiber officinale extract exhibits antidiabetic potential via modulating glucose uptake, protein glycation and inhibiting adipocyte differentiation: An in vitro study. J Sci Food Agric. 92:1948–1955. 2012.PubMed/NCBI View Article : Google Scholar
13	Suk S, Seo SG, Yu JG, Yang H, Jeong E, Jang YJ, Yaghmoor SS, Ahmed Y, Yousef JM, Abualnaja KO, et al: A bioactive constituent of ginger, 6-shogaol, prevents adipogenesis and stimulates lipolysis in 3T3-L1 Adipocytes. J Food Biochem. 40:84–90. 2016.
14	Wang J, Zhang L, Dong L, Hu X, Feng F and Chen F: 6-Gingerol, a functional polyphenol of ginger, promotes browning through an AMPK-Dependent Pathway in 3T3-L1 Adipocytes. J Agric Food Chem. 67:14056–14065. 2019.PubMed/NCBI View Article : Google Scholar
15	Cheng Z, Xiong X, Zhou Y, Wu F, Shao Q, Dong R, Liu Q, Li L and Chen G: 6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice. Biomed Pharmacother. 146(112491)2022.PubMed/NCBI View Article : Google Scholar
16	Hong KH, Um MY, Ahn J and Ha TY: 6-Gingerol ameliorates adiposity and inflammation in adipose tissue in high fat diet-induced obese mice: Association with regulating of adipokines. Nutrients. 15(3457)2023.PubMed/NCBI View Article : Google Scholar
17	Jiao W, Mi S, Sang Y, Jin Q, Chitrakar B, Wang X and Wang S: Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol. Food Chem. 374(131755)2022.PubMed/NCBI View Article : Google Scholar
18	Park SH, Jung SJ, Choi EK, Ha KC, Baek HI, Park YK, Han KH, Jeong SY, Oh JH, Cha YS, et al: The effects of steamed ginger ethanolic extract on weight and body fat loss: A randomized, double-blind, placebo-controlled clinical trial. Food Sci Biotechnol. 29:265–273. 2020.PubMed/NCBI View Article : Google Scholar
19	Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, Feng MR and Brenner DE: Pharmacokinetics of 6-Gingerol, 8-Gingerol, 10-Gingerol, and 6-Shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 17:1930–1936. 2008.PubMed/NCBI View Article : Google Scholar
20	Suk S, Kwon GT, Lee E, Jang WJ, Yang H, Kim JH, Thimmegowda NR, Chung MY, Kwon JY, Yang S, et al: Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice. Mol Nutr Food Res. 61(10.1002/mnfr.201700139)2017.PubMed/NCBI View Article : Google Scholar
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
22	Kraus NA, Ehebauer F, Zapp B, Rudolphi B, Kraus BJ and Kraus D: Quantitative assessment of adipocyte differentiation in cell culture. Adipocyte. 5:351–358. 2016.PubMed/NCBI View Article : Google Scholar
23	Quintero-Fabián S, Ortuño-Sahagún D, Vázquez-Carrera M and López-Roa RI: Alliin, a garlic (Allium sativum) compound, prevents LPS-induced inflammation in 3T3-L1 adipocytes. Mediators Inflamm. 2013(381815)2013.PubMed/NCBI View Article : Google Scholar
24	Lee GH, Peng C, Jeong SY, Park SA, Lee HY, Hoang TH, Kim J and Chae HJ: Ginger extract controls mTOR-SREBP1-ER stress-mitochondria dysfunction through AMPK activation in obesity model. J Funct Foods. 87(104628)2021.
25	Ahn EK and Oh JS: Inhibitory effect of galanolactone isolated from Zingiber officinale Roscoe extract on adipogenesis in 3T3-L1 cells. J Korean Soc Appl Biol Chem. 55:63–68. 2012.
26	Madsen MS, Siersbæk R, Boergesen M, Nielsen R and Mandrup S: Peroxisome proliferator-activated receptor γ and C/EBPα synergistically activate key metabolic adipocyte genes by assisted loading. Mol Cell Biol. 34:939–954. 2014.PubMed/NCBI View Article : Google Scholar
27	Liu GY and Sabatini DM: mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 21:183–203. 2020.PubMed/NCBI View Article : Google Scholar
28	Lee PL, Jung SM and Guertin DA: . The complex roles of mechanistic target of rapamycin in adipocytes and beyond. Trends Endocrinol Metab. 28:319–339. 2017.PubMed/NCBI View Article : Google Scholar
29	Ricoult SJ and Manning BD: The multifaceted role of mTORC1 in the control of lipid metabolism. EMBO Rep. 14:242–251. 2013.PubMed/NCBI View Article : Google Scholar
30	Lee PL, Jung SM and Guertin DA: The complex roles of mechanistic target of rapamycin in adipocytes and beyond. Trends Endocrinol Metab. 28:319–339. 2017.PubMed/NCBI View Article : Google Scholar
31	Cave E and Crowther NJ: The Use of 3T3-L1 murine preadipocytes as a model of adipogenesis. Methods Mol Biol. 1916:263–272. 2019.PubMed/NCBI View Article : Google Scholar
32	Okamoto M, Irii H, Tahara Y, Ishii H, Hirao A, Udagawa H, Hiramoto M, Yasuda K, Takanishi A, Shibata S and Shimizu I: Synthesis of a new [6]-gingerol analogue and its protective effect with respect to the development of metabolic syndrome in mice fed a high-fat diet. J Med Chem. 54:6295–6304. 2011.PubMed/NCBI View Article : Google Scholar
33	Liang T, Xing Z, Jiang L and Zhu JJ: Tailoring nanoparticles for targeted drug delivery: From organ to subcellular level. VIEW. 2(20200131)2021.
34	Geraili A, Xing M and Mequanint K: Design and fabrication of drug-delivery systems toward adjustable release profiles for personalized treatment. VIEW. 2(20200126)2021.