Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. EECM Preparation, Identification, and Standardization
2.2. Differentiation of Adipocytes
2.3. Cell Viability
2.4. Oil Red O Staining
2.5. Western Blot Analysis
2.6. MCE Determination
2.7. HFD-Induced Obese Animals Experiments
2.8. Body Fat Composition Analysis
2.9. Hematoxylin and Eosin (H&E) Staining Analysis
2.10. Biochemical Examination of Blood Plasma
2.11. Genomic DNA Extraction and Microbiome Taxonomic Profiling (MTP)
2.12. Statistical Analysis
3. Results
3.1. Identification of Quercitrin and Standardization of EECM via UPLC–High-Resolution Mass Spectrometry (HR/MS)
3.2. EECM Inhibits Differentiation and Regulates Lipogenesis and Adipogenesis via AMPK Pathway in 3T3-L1 Preadipocytes
3.3. EECM Suppresses MCE during Early Differentiation of 3T3-L1 Preadipocytes
3.4. EECM Obstructs the Body Weight Gain of HFD-Induced Obese Mice
3.5. EECM Changes the Fat Composition in HFD-Induced Obese Mice
3.6. EECM Alleviates the Production of Insulin, Adipokines, and Lipid Parameters in Blood Plasma of HFD-Induced Obese Mice
3.7. EECM Prevents Hypertrophy of Lipid Droplets and Adipogenesis in Subcutaneous Fat of HFD-Induced Obese Mice
3.8. EECM Ameliorates Lipid Accumulation in Liver Tissue of HFD-Induced Obese Mice
3.9. EECM Upregulates Thermogenic-Mediated Proteins Levels in Brown Adipose Tissue (BAT) of HFD-Induced Obese Mice
3.10. EECM Regulates the Gut Microbiota Composition and Alleviates the Dysbiosis in HFD-Induced Obese Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Haslam, D.W.; James, W.P. Obesity. Lancet 2005, 366, 1197–1209. [Google Scholar] [CrossRef]
- Geum, N.G.; Son, H.J.; Yeo, J.H.; Yu, J.H.; Choi, M.Y.; Lee, J.W.; Baek, J.K.; Jeong, J.B. Anti-obesity activity of Heracleum moellendorffii root extracts in 3T3-L1 adipocytes. Food Sci. Nutr. 2021, 9, 5939–5945. [Google Scholar] [CrossRef] [PubMed]
- Kopelman, P.G. Obesity as a medical problem. Nature 2000, 404, 635–643. [Google Scholar] [CrossRef] [PubMed]
- Jakab, J.; Miskic, B.; Miksic, S.; Juranic, B.; Cosic, V.; Schwarz, D.; Vcev, A. Adipogenesis as a Potential Anti-Obesity Target: A Review of Pharmacological Treatment and Natural Products. Diabetes Metab. Syndr. Obes. 2021, 14, 67–83. [Google Scholar] [CrossRef] [PubMed]
- Tang, Q.Q.; Otto, T.C.; Lane, M.D. Mitotic clonal expansion: A synchronous process required for adipogenesis. Proc. Natl. Acad. Sci. USA 2003, 100, 44–49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carling, D. AMPK signalling in health and disease. Curr. Opin. Cell Biol. 2017, 45, 31–37. [Google Scholar] [CrossRef]
- Han, H.S.; Lee, H.H.; Gil, H.S.; Chung, K.S.; Kim, J.K.; Kim, D.H.; Yoon, J.; Chung, E.K.; Lee, J.K.; Yang, W.M.; et al. Standardized hot water extract from the leaves of Hydrangea serrata (Thunb.) Ser. alleviates obesity via the AMPK pathway and modulation of the gut microbiota composition in high fat diet-induced obese mice. Food Funct. 2021, 12, 2672–2685. [Google Scholar] [CrossRef]
- Fang, K.; Wu, F.; Chen, G.; Dong, H.; Li, J.; Zhao, Y.; Xu, L.; Zou, X.; Lu, F. Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells. BMC Complement. Altern. Med. 2019, 19, 255. [Google Scholar] [CrossRef] [Green Version]
- Fenzl, A.; Kiefer, F.W. Brown adipose tissue and thermogenesis. Horm. Mol. Biol. Clin. Investig. 2014, 19, 25–37. [Google Scholar] [CrossRef]
- Gesta, S.; Tseng, Y.H.; Kahn, C.R. Developmental origin of fat: Tracking obesity to its source. Cell 2007, 131, 242–256. [Google Scholar] [CrossRef]
- Vijgen, G.H.; Bouvy, N.D.; Teule, G.J.; Brans, B.; Schrauwen, P.; van Marken Lichtenbelt, W.D. Brown adipose tissue in morbidly obese subjects. PLoS ONE 2011, 6, e17247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ouellet, V.; Routhier-Labadie, A.; Bellemare, W.; Lakhal-Chaieb, L.; Turcotte, E.; Carpentier, A.C.; Richard, D. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J. Clin. Endocrinol. Metab. 2011, 96, 192–199. [Google Scholar] [CrossRef]
- Magne, F.; Gotteland, M.; Gauthier, L.; Zazueta, A.; Pesoa, S.; Navarrete, P.; Balamurugan, R. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients 2020, 12, 1474. [Google Scholar] [CrossRef]
- Stojanov, S.; Berlec, A.; Strukelj, B. The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms 2020, 8, 1715. [Google Scholar] [CrossRef] [PubMed]
- Lim, S.H.; Lee, J. Methanol Extract of Cassia mimosoides var. nomame Attenuates Myocardial Injury by Inhibition of Apoptosis in a Rat Model of Ischemia-Reperfusion. Prev. Nutr. Food Sci. 2012, 17, 177–183. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, K.-H.; Lee, J.-W. Methanol Extract of Cassia mimosoides var. nomame and Its Ethyl Acetate Fraction Attenuate Brain Damage by Inhibition of Apoptosis in a Rat Model of Ischemia-Reperfusion. J. Food Sci. Nutr. 2010, 15, 255–261. [Google Scholar] [CrossRef]
- Lee, S.Y.; Chung, K.S.; Son, S.R.; Lee, S.Y.; Jang, D.S.; Lee, J.K.; Kim, H.J.; Na, C.S.; Lee, S.H.; Lee, K.T. A Botanical Mixture Consisting of Inula japonica and Potentilla chinensis Relieves Obesity via the AMPK Signaling Pathway in 3T3-L1 Adipocytes and HFD-Fed Obese Mice. Nutrients 2022, 14, 3685. [Google Scholar] [CrossRef] [PubMed]
- Saito, M.; Matsushita, M.; Yoneshiro, T.; Okamatsu-Ogura, Y. Brown Adipose Tissue, Diet-Induced Thermogenesis, and Thermogenic Food Ingredients: From Mice to Men. Front. Endocrinol. (Lausanne) 2020, 11, 222. [Google Scholar] [CrossRef] [Green Version]
- Matsuda, M.; Shimomura, I. Increased oxidative stress in obesity: Implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes. Res. Clin. Pract. 2013, 7, e330–e341. [Google Scholar] [CrossRef]
- Nam, G.E.; Kim, Y.H.; Han, K.; Jung, J.H.; Rhee, E.J.; Lee, S.S.; Kim, D.J.; Lee, K.W.; Lee, W.Y.; Korean Society for the Study of Obesity. Obesity Fact Sheet in Korea, 2019: Prevalence of Obesity and Abdominal Obesity from 2009 to 2018 and Social Factors. J. Obes. Metab. Syndr. 2020, 29, 124–132. [Google Scholar] [CrossRef]
- Osadebe, P.O.; Odoh, E.U.; Uzor, P.F. Natural Products as Potential Sources of Antidiabetic Drugs. J. Pharm. Res. Int. 2014, 4, 2075–2095. [Google Scholar] [CrossRef]
- Rena, G.; Hardie, D.G.; Pearson, E.R. The mechanisms of action of metformin. Diabetologia 2017, 60, 1577–1585. [Google Scholar] [CrossRef] [Green Version]
- Koh, H.E.; Cao, C.; Mittendorfer, B. Insulin Clearance in Obesity and Type 2 Diabetes. Int. J. Mol. Sci. 2022, 23, 596. [Google Scholar] [CrossRef]
- Havel, P.J.; Kasim-Karakas, S.; Mueller, W.; Johnson, P.R.; Gingerich, R.L.; Stern, J.S. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: Effects of dietary fat content and sustained weight loss. J. Clin. Endocrinol. Metab. 1996, 81, 4406–4413. [Google Scholar] [CrossRef] [Green Version]
- 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]
- Achari, A.E.; Jain, S.K. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int. J. Mol. Sci. 2017, 18, 1321. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kawano, J.; Arora, R. The role of adiponectin in obesity, diabetes, and cardiovascular disease. J. Cardiometab. Syndr. 2009, 4, 44–49. [Google Scholar] [CrossRef] [PubMed]
- Farmer, S.R. Transcriptional control of adipocyte formation. Cell Metab. 2006, 4, 263–273. [Google Scholar] [CrossRef] [Green Version]
- Lefterova, M.I.; Lazar, M.A. New developments in adipogenesis. Trends Endocrinol. Metab. 2009, 20, 107–114. [Google Scholar] [CrossRef]
- Moseti, D.; Regassa, A.; Kim, W.K. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int. J. Mol. Sci. 2016, 17, 124. [Google Scholar] [CrossRef]
- Wu, Z.; Rosen, E.D.; Brun, R.; Hauser, S.; Adelmant, G.; Troy, A.E.; McKeon, C.; Darlington, G.J.; Spiegelman, B.M. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol. Cell 1999, 3, 151–158. [Google Scholar] [CrossRef]
- Xiao, X.; Song, B.L. SREBP: A novel therapeutic target. Acta Biochim. Biophys. Sin. (Shanghai) 2013, 45, 2–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sekiya, M.; Yahagi, N.; Matsuzaka, T.; Takeuchi, Y.; Nakagawa, Y.; Takahashi, H.; Okazaki, H.; Iizuka, Y.; Ohashi, K.; Gotoda, T.; et al. SREBP-1-independent regulation of lipogenic gene expression in adipocytes. J. Lipid Res. 2007, 48, 1581–1591. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Crewe, C.; Zhu, Y.; Paschoal, V.A.; Joffin, N.; Ghaben, A.L.; Gordillo, R.; Oh, D.Y.; Liang, G.; Horton, J.D.; Scherer, P.E. SREBP-regulated adipocyte lipogenesis is dependent on substrate availability and redox modulation of mTORC1. JCI Insight 2019, 5, e129397. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.; Li, Z.; Li, W.; Shan, Z.; Zhu, W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can. J. Physiol. Pharmacol. 2011, 89, 793–799. [Google Scholar] [CrossRef] [PubMed]
- Hardie, D.G.; Carling, D. The AMP-activated protein kinase--fuel gauge of the mammalian cell? Eur. J. Biochem. 1997, 246, 259–273. [Google Scholar] [CrossRef]
- Student, A.K.; Hsu, R.Y.; Lane, M.D. Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. J. Biol. Chem. 1980, 255, 4745–4750. [Google Scholar] [CrossRef]
- Kahn, B.B.; Alquier, T.; Carling, D.; Hardie, D.G. AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005, 1, 15–25. [Google Scholar] [CrossRef] [Green Version]
- Fajas, L. Adipogenesis: A cross-talk between cell proliferation and cell differentiation. Ann. Med. 2003, 35, 79–85. [Google Scholar] [CrossRef]
- Tang, Q.Q.; Lane, M.D. Adipogenesis: From stem cell to adipocyte. Annu. Rev. Biochem. 2012, 81, 715–736. [Google Scholar] [CrossRef]
- Han, H.S.; Chung, K.S.; Shin, Y.K.; Lee, S.H.; Lee, K.T. Standardized Hydrangea serrata (Thunb.) Ser. Extract Ameliorates Obesity in db/db Mice. Nutrients 2021, 13, 3624. [Google Scholar] [CrossRef] [PubMed]
- Oh, J.M.; Chun, S. Ginsenoside CK Inhibits the Early Stage of Adipogenesis via the AMPK, MAPK, and AKT Signaling Pathways. Antioxidants 2022, 11, 1890. [Google Scholar] [CrossRef] [PubMed]
- Qu, Y.; Chen, S.; Zhou, L.; Chen, M.; Li, L.; Ni, Y.; Sun, J. The different effects of intramuscularly-injected lactate on white and brown adipose tissue in vivo. Mol. Biol. Rep. 2022, 49, 8507–8516. [Google Scholar] [CrossRef] [PubMed]
- Klingenberg, M.; Huang, S.G. Structure and function of the uncoupling protein from brown adipose tissue. Biochim. Biophys. Acta 1999, 1415, 271–296. [Google Scholar] [CrossRef] [Green Version]
- Puigserver, P.; Wu, Z.; Park, C.W.; Graves, R.; Wright, M.; Spiegelman, B.M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998, 92, 829–839. [Google Scholar] [CrossRef] [Green Version]
- Haemmerle, G.; Moustafa, T.; Woelkart, G.; Buttner, S.; Schmidt, A.; van de Weijer, T.; Hesselink, M.; Jaeger, D.; Kienesberger, P.C.; Zierler, K.; et al. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-alpha and PGC-1. Nat. Med. 2011, 17, 1076–1085. [Google Scholar] [CrossRef] [Green Version]
- You, M.; Rogers, C.Q. Adiponectin: A key adipokine in alcoholic fatty liver. Exp. Biol. Med. (Maywood) 2009, 234, 850–859. [Google Scholar] [CrossRef]
- Chen, X.Y.; Cai, C.Z.; Yu, M.L.; Feng, Z.M.; Zhang, Y.W.; Liu, P.H.; Zeng, H.; Yu, C.H. LB100 ameliorates nonalcoholic fatty liver disease via the AMPK/Sirt1 pathway. World J. Gastroenterol. 2019, 25, 6607–6618. [Google Scholar] [CrossRef]
- Abenavoli, L.; Scarpellini, E.; Colica, C.; Boccuto, L.; Salehi, B.; Sharifi-Rad, J.; Aiello, V.; Romano, B.; De Lorenzo, A.; Izzo, A.A.; et al. Gut Microbiota and Obesity: A Role for Probiotics. Nutrients 2019, 11, 2690. [Google Scholar] [CrossRef] [Green Version]
- Castaner, O.; Goday, A.; Park, Y.M.; Lee, S.H.; Magkos, F.; Shiow, S.T.E.; Schroder, H. The Gut Microbiome Profile in Obesity: A Systematic Review. Int. J. Endocrinol. 2018, 2018, 4095789. [Google Scholar] [CrossRef]
- Liu, B.N.; Liu, X.T.; Liang, Z.H.; Wang, J.H. Gut microbiota in obesity. World J. Gastroenterol. 2021, 27, 3837–3850. [Google Scholar] [CrossRef] [PubMed]
- Cuevas-Sierra, A.; Ramos-Lopez, O.; Riezu-Boj, J.I.; Milagro, F.I.; Martinez, J.A. Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications. Adv. Nutr. 2019, 10, S17–S30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Human Microbiome Project, C. Structure, function and diversity of the healthy human microbiome. Nature 2012, 486, 207–214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pedersen, R.; Ingerslev, H.C.; Sturek, M.; Alloosh, M.; Cirera, S.; Christoffersen, B.O.; Moesgaard, S.G.; Larsen, N.; Boye, M. Characterisation of gut microbiota in Ossabaw and Gottingen minipigs as models of obesity and metabolic syndrome. PLoS ONE 2013, 8, e56612. [Google Scholar] [CrossRef]
Lipid Profiles | CON | HFD | Orlistat (20 mg/kg) | EECM (100 mg/kg) | EECM (300 mg/kg) |
---|---|---|---|---|---|
TC (mg/dL) | 104.88 ± 5.08 | 157.00 ± 3.14 # | 130.25 ± 13.19 ** | 145.00 ± 6.54 | 142.38 ± 4.04 * |
TG (mg/dL) | 55.50 ± 4.18 | 112.25 ± 5.87 # | 67.75 ± 8.35 ** | 70.00 ± 9.14 ** | 63.00 ± 9.58 *** |
LDL (mg/dL) | 10.13 ± 0.81 | 15.00 ± 0.50 # | 11.88 ± 0.91 * | 12.63 ± 0.53 | 12.63 ± 0.46 |
HDL (mg/dL) | 85.75 ± 2.10 | 92.88 ± 4.97 | 113.13 ± 9.27 | 102.25 ± 3.22 | 100.50 ± 2.05 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 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 (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Heo, S.-W.; Chung, K.-S.; Yoon, Y.-S.; Kim, S.-Y.; Ahn, H.-S.; Shin, Y.-K.; Lee, S.-H.; Lee, K.-T. Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice. Nutrients 2023, 15, 613. https://doi.org/10.3390/nu15030613
Heo S-W, Chung K-S, Yoon Y-S, Kim S-Y, Ahn H-S, Shin Y-K, Lee S-H, Lee K-T. Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice. Nutrients. 2023; 15(3):613. https://doi.org/10.3390/nu15030613
Chicago/Turabian StyleHeo, So-Won, Kyung-Sook Chung, Young-Seo Yoon, Soo-Yeon Kim, Hye-Shin Ahn, Yu-Kyong Shin, Sun-Hee Lee, and Kyung-Tae Lee. 2023. "Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice" Nutrients 15, no. 3: 613. https://doi.org/10.3390/nu15030613