Extract of Acalypha australis L. inhibits lipid accumulation and ameliorates HFD-induced obesity in mice through regulating adipose differentiation by decreasing PPARγ and CEBP/α expression
Background: Obesity is a principal risk factor for the development of type 2 diabetes and cardiovascular diseases. Natural plants and/or foods play an important role in the management of obesity. Acalypha australis L. (AAL) is a kind of potherb popular among Asian populations, and it is also consumed as a food ingredient and traditional herbal medicine.
Objective: We investigated the effects of water extract from AAL on high-fat-diet (HFD)-induced obese mice and 3T3-L1 adipocytes to develop a new functional food material.
Design: Nine-week-old male mice were randomly divided into control (chow diet, n = 6) and HFD (n = 30) group. From 12-weeks onward, mice in the HFD group were further separated into model (saline, 6 mL/ kg), simvastatin (0.11 mg/mL, 6 mL/kg), and AAL treatment (low, middle, and high dosage: 300, 600, and 900 mg/kg) group, with 6 animals per group, while mice in the control group were treated with saline (6 mL/ kg). Food intake, body/fat weight, liver/kidney indexes, and lipid profiles were determined. Tissues were fixed with formalin for pathological examination. Western blotting and PCR were performed to evaluate the protein and mRNA expression in 3T3-L1 adipocytes. Oil Red O staining was used to determine lipid accumulation.
Results: AAL administration significantly suppressed body weight gain, and reduced fat pad weight and Lee’s index in obese mice, but had no effect on liver/kidney index. AAL also reduced serum cholesterol, triglyceride, and LDL-C and increased HDL-C levels. Histological analysis revealed that AAL significantly ameliorated lipid accumulation in the liver and subcutaneous adipose tissue. In vitro, Oil Red O staining showed that AAL inhibited adipose differentiation by down-regulating the gene and protein expression of PPARγ and C/EBPα. AAL also reversed HFD-induced intestinal dysbacteriosis.
Conclusion: AAL water-soluble extract has a significant anti-adipogenic effect in the HFD-induced obese mice model.
- Bluher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 2019; 15(5): 288–98. doi: 10.1038/s41574-019-0176-8
- World Health Organization. Obesity and overweight 2020. Available from: https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight [cited 17 February 2021].
- Ryan DH, Kahan S. Guideline recommendations for obesity management. Med Clin North Am 2018; 102(1): 49–63. doi: 10.1016/j.mcna.2017.08.006
- Ioannides-Demos LL, Proietto J, Tonkin AM, McNeil JJ. Safety of drug therapies used for weight loss and treatment of obesity. Drug Saf 2006; 29(4): 277–302. doi: 10.2165/00002018-200629040-00001
- McGee M, Whitehead N, Martin J, Collins N. Drug-associated pulmonary arterial hypertension. Clin Toxicol (Phila) 2018; 56(9): 801–9. doi: 10.1080/15563650.2018.1447119
- Kim HJ, Joe HI, Zhang Z, Woo Lee S, Lee KY, Kook YB, et al. Anti-inflammatory effect of Acalypha australis L. via suppression of NF-kappaB signaling in LPS-stimulated RAW 264.7 macrophages and LPS-induced septic mice. Mol Immunol 2020; 119: 123–31. doi: 10.1016/j.molimm.2020.01.010
- Shin JA, Kim JJ, Choi ES, Shim JH, Ryu MH, Kwon KH, et al. In vitro apoptotic effects of methanol extracts of Dianthus chinensis and Acalypha australis L. targeting specificity protein 1 in human oral cancer cells. Head Neck-J Sci Spec 2013; 35(7): 992–8. doi: 10.1002/hed.23072
- Li H, Ding Z, Sun L, Zeng J. Experimental study on antitussive and expectorant effects of Acalyph Aaustralis L. Lishizhen Med Mater Med Res 2009; 4: 856–7. doi:10.3969/j.issn.1008-0805.2009.04.046
- Deng L, Hu J. Acalypha decoction in prevention and treatment of trinitrobenzene sulfonic acid induced ulcerative colitis in rats. Acad J Sec Milit Med Univ 2005; 5: 535–8. doi: 10.16781/j.0258-879x.2005.05.022
- Deng L, Li F, Zou H, Chen J, Hu J. Polar compounds of Acalypha australis L. on TNBS-induced ulcerative colitis. Chin Tradit Patent Med 2007; 7: 969–71. doi: 10.3969/j.issn.1001-1528.2007.07.010
- Lei-Lei M. Determination of glycyrrhizic acid and berberine in Xiancaihuangliansu capsules by HPLC. Chin Drug Stand 2013; 1: 21–23. doi:10.19778/j.chp.2013.01.007
- Cui M, Xu J, Xu X, Xiang F, Liu J. Optimization of ultrasonic-assisted alkali extraction and acid precipitation technology for total flavonoids from Acalypha australis. China J Exp Tradit Med Formul 2013; 22. doi: 10.11653/syfj2013220038
- Chen YF, FSY, Jin L, Li YH, Zhang Y. Molecular mechanisms of the fat-lowering and weight losing properties of dietary flavonoids: a review. J Chin Instit Food Sci Technol 2019; 10. doi: 10.16429/j.1009-7848.2019.10.038
- Yu JJ, Su J, Yan MQ, Lou ZH, Lyu GY. Correlation between lipid-lowering efficacy and components of Pericarpium Citri Reticulatae. Zhongguo Zhong Yao Za Zhi 2019; 44(15): 3335–42. doi: 10.19540/j.cnki.cjcmm.20190523.304
- Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 2011; 12(11): 722–34. doi: 10.1038/nrm3198
- Satoh A, Stein L, Imai S. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol 2011; 206: 125–62. doi: 10.1007/978-3-642-21631-2_7
- Auwerx J, Cock TA, Knouff C. PPAR-gamma: a thrifty transcription factor. Nucl Recept Signal. 2003; 1: e006. doi: 10.1621/nrs.01006
- Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003; 361(9356): 512–19. doi: 10.1016/S0140-6736(03)12489-0
- Chen F, Wen Q, Jiang J, Li HL, Tan YF, Li YH, et al. Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs? J Ethnopharmacol 2016; 179: 253–64. doi: 10.1016/j.jep.2015.12.031
- Xiao Y, Meng L, Lei Y, Wan D. Characterization and microscopic identification of acalyph aaustralis L. J Chin Med Mater 2000; 8: 443–5. doi: 10.3321/j.issn:1001-4454.2000.08.007
- Ning L, Chen M, Liu M. Characteristics and cultivation techniques of Acalyph aaustralis L. Modern Agric Sci Technol 2012; 6: 147–8. doi: 10.3969/j.issn.1007-5739.2012.06.090
- Wang CC, Yen JH, Cheng YC, Lin CY, Hsieh CT, Gau RJ, et al. Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles. Food Nutr Res 2017; 61(1): 1379861. doi: 10.1080/16546628.2017.1379861
- Li F, Gao C, Yan P, Zhang M, Wang YH, Hu Y, et al. EGCG reduces obesity and white adipose tissue gain partly through AMPK activation in mice. Front Pharmacol 2018; 9. doi: 10.3389/fphar.2018.01366
- Brown GT, Kleiner DE. Histopathology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Metabolism 2016; 65(8): 1080–6. doi: 10.1016/j.metabol.2015.11.008
- Yan Y, Liu J, Zhao X, Cheng H, Huang G, Mi J, et al. Abdominal visceral and subcutaneous adipose tissues in association with cardiometabolic risk in children and adolescents: the China Child and Adolescent Cardiovascular Health (CCACH) study. BMJ Open Diabetes Res Care 2019; 7(1): e000824. doi: 10.1136/bmjdrc-2019-000824
- Pomeroy E, Mushrif-Tripathy V, Kulkarni B, Kinra S, Stock JT, Cole TJ, et al. Estimating body mass and composition from proximal femur dimensions using dual energy x-ray absorptiometry. Archaeol Anthrop Sci 2019; 11(5): 2167–79. doi: 10.1007/s12520-018-0665-z
- Stojanovi O, Kieser S, Trajkovski M. Common traits between the beige fat-inducing stimuli. Curr Opin Cell Biol 2018; 55: 67–73. doi: 10.1016/j.ceb.2018.05.011
- Vishvanath L, Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity. J Clin Invest 2019; 129(10): 4022–31. doi: 10.1172/Jci129191
- Wei X, Lin X, Li X, Zhao H, Liu W. Comparison of gallic acid and total flavones content in Guizhou Acalypha australis from the different harvest time and different parts. West China J Pharmaceut Sci 2014; 5: 3. doi: 10.13375/j.cnki.wcjps.2014.05.032
- Huang W, Wu L, Yin W, Jin H, He M, Zhou B. Determination of protocatechuic acid and protocatechuic aldehyde in Acalypha australis L. by HPLC. Lishizhen Med Mater Med Res 2016; 27: 1750–52. doi: 10.3969/j.issn.1008-0805.2016.07.011
- Luo Q, Zhou G, Liao A, Ggao Y. Simultaneous determination of 7 active components in Acalypha by ultrasonic assisted extraction and high performance liquid chromatography. China J Tradit Chinese Med Pharm 2018; 33: 5.
- Wei X, Lin X, Li X, Zhao H, Lin W. Different processing methods of Acalypha australis in the habitats. Chinese Tradit Patent Med 2014; 36: 4. doi: 10.3969/j.issn.1001-1528.2014.05.031
- Kma L. Plant extracts and plant-derived compounds: promising players in a countermeasure strategy against radiological exposure. Asian Pac J Cancer Prev 2014; 15(6): 2405–25. doi: 10.7314/apjcp.2014.15.6.2405
- Liu XM, Liu YJ, Huang Y, Yu HJ, Yuan S, Tang BW, et al. Dietary total flavonoids intake and risk of mortality from all causes and cardiovascular disease in the general population: a systematic review and meta-analysis of cohort studies. Mol Nutr Food Res 2017; 61(6). doi: 10.1002/mnfr.201601003
- Fu Y, Chen J, Li YJ, Zheng YF, Li P. Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice. Food Chem 2013; 141(2): 1063–71. doi: 10.1016/j.foodchem.2013.03.089
- Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008; 88(1): 38–50. doi: 10.1093/ajcn/88.1.38
- Tohill BC, Seymour J, Serdula M, Kettel-Khan L, Rolls BJ. What epidemiologic studies tell us about the relationship between fruit and vegetable consumption and body weight. Nutr Rev 2004; 62(10): 365–74. doi: 10.1301/nr.2004.oct.365-374
- Xiao-Mei WC-JLG-FLJH. Study on extraction and function of scavenging hydroxyl free radical of flavonoids from Acalypha australis L. Chin J Spectrosc Lab 2010; 3: 797–802. doi: 10.3969/j.issn.1004-8138.2010.03.002
- Johannsen DL, Tchoukalova Y, Tam CS, Covington JD, Xie WT, Schwarz JM, et al. Effect of 8 weeks of overfeeding on ectopic fat deposition and insulin sensitivity: testing the ‘adipose tissue expandability’ hypothesis. Diabetes Care 2014; 37(10): 2789–97. doi: 10.2337/dc14-0761
- Lehrke M, Lazar MA. The many faces of PPAR gamma. Cell 2005; 123(6): 993–9. doi: 10.1016/j.cell.2005.11.026
- Tontonoz P, Spiegelman BM. Fat and beyond: the diverse biology of PPAR gamma. Annu Rev Biochem 2008; 77: 289–312. doi: 10.1146/annurev.biochem.77.061307.091829
- Garin-Shkolnik T, Rudich A, Hotamisligil GS, Rubinstein M. FABP4 attenuates PPAR gamma and adipogenesis and is inversely correlated with PPARg in adipose tissues. Diabetes 2014; 63(3): 900–11. doi: 10.2337/db13-0436
- Ohlsson E, Hasemann MS, Willer A, Lauridsen FK, Rapin N, Jendholm J, et al. Initiation of MLL-rearranged AML is dependent on C/EBPalpha. J Exp Med 2014; 211(1): 5–13. doi: 10.1084/jem.20130932
- Wang H, Zan LS, Wang HB, Gong C, Fu CZ. Cloning, expression analysis and sequence prediction of the CCAAT/enhancer-binding protein alpha gene of Qinchuan cattle. Genet Mol Res 2012; 11(2): 1651–61. doi: 10.4238/2012.June.15.14
- Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, et al. C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. Proc Natl Acad Sci U S A 2001; 98(22): 12532–7. doi: 10.1073/pnas.211416898
- Qiao Y, Sun J, Xia SF, Tang X, Shi YH, Le GW. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity. Food Funct 2014; 5(6): 1241–9. doi: 10.1039/c3fo60630a
- Xu H, Zhao CF, Li YT, Liu RY, Ao MZ, Li FC, et al. The ameliorative effect of the Pyracantha fortuneana (Maxim.) H. L. Li extract on intestinal barrier dysfunction through modulating glycolipid digestion and gut microbiota in high fat diet-fed rats. Food Funct 2019; 10(10): 6517–32. doi: 10.1039/c9fo01599j
- Wang Y, Fei YQ, Liu LR, Xiao YH, Pang YL, Kang JH, et al. Polygonatum odoratum polysaccharides modulate gut microbiota and mitigate experimentally induced obesity in rats. Int J Mol Sci 2018; 19(11). doi: 10.3390/ijms19113587
- Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007; 50(11): 2374–83. doi: 10.1007/s00125-007-0791-0
- Quan LH, Zhang C, Dong M, Jiang J, Xu H, Yan C, et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation. Gut 2019. doi: 10.1136/gutjnl-2019-319114
- Martinez I, Wallace G, Zhang C, Legge R, Benson AK, Carr TP, et al. Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Appl Environ Microbiol 2009; 75(12): 4175–84. doi: 10.1128/AEM.00380-09
- Zhu K, Tan F, Mu J, Yi R, Zhou X, Zhao X. Anti-obesity effects of Lactobacillus fermentum CQPC05 isolated from sichuan pickle in high-fat diet-induced obese mice through PPAR-alpha signaling pathway. Microorganisms 2019; 7(7). doi: 10.3390/microorganisms7070194
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