BACKGROUND: Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro. METHODS: Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes. RESULTS: XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells. CONCLUSION: XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity.

Department of Endocrinology Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China

Department of Endocrinology Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University Urumqi 830000 China

Hospital Administration Office China Academy of Chinese Medical Sciences Beijing 100700 China

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Medanić D, Pucarin-Cvetković J. Obesity - a public health problem and challenge. Acta Med Croatica 2012;66(5):347-55.

Piché ME, Tchernof A, Després JP. Obesity Phenotypes, Diabetes, and Cardiovascular Diseases. Circ Res 2020;126(11):1477-500. DOI

Caballero B. Humans against Obesity: Who Will Win? Adv Nutr 2019;10(suppl_1):S4-S9. DOI

Zebisch K, Voigt V, Wabitsch M, Brandsch M. Protocol for effective differentiation of 3T3-L1 cells to adipocytes. Anal Biochem 2012;425(1):88-90. DOI

Bu S, Yuan CY, Xue Q, Chen Y, Cao F. Bilobalide Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway. Molecules 2019;24(19):3503. DOI

Liu X, Liu XN, Li TJ, Liu B. Research Progress of the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2017;39(5):727-31.

Lee M, Sorn SR, Lee Y, Kang I. Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes. Int J Mol Sci 2019;20(1):160. DOI

Bhatt-Wessel B, Jordan TW, Miller JH, Peng L. Role of DGAT enzymes in triacylglycerol metabolism. Arch Biochem Biophys 2018;655:1-11. DOI

Cerk IK, Wechselberger L, Oberer M. Adipose Triglyceride Lipase Regulation: An Overview. Curr Protein Pept Sci 2018;19(2):221-33. DOI

Quiroga AD, Lehner R. Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly. Biochem Pharmacol 2018;155:233-41. DOI

Chang E, Kim CY. Natural Products and Obesity: A Focus on the Regulation of Mitotic Clonal Expansion during Adipogenesis. Molecules 2019;24(6):1157. DOI

Qin PJ, Min LI, Lian FM, Zhen Z, Chang B, Xiu-Yang LI, Tong XL. Clinical observation of 86 cases of obesity treated by Xiaogao Jiangzhuo method. J Shandong Univ Trad Chin Med 2011;35:23-7.

Yang H, Jin Z, Gu C, Wei Y. Professor Tong Xiaolin's experience in treating moderate-to-severe fatty liver with virgate wormwood herb, hongqu and unprocessed rhubarb root. Jilin J Chin Med 2021;41(01):19-21. DOI

Wen ZG, Shao MS, Zhao LH. Study on the clinical application and dosage of hawthorn fruit. J Changchun Univ Chin Med 2021;37(04):741-4.

Zheng YJ, Zhang LL, Ding QY, Lin JR, Gu CJ. Experience in the Treatment of Hyperlipemia with Massa Medicata Fermentata,Rhizoma Pinelliae Fermentata and Fermentum Rubrum-Three Prescription by Professor TONG Xiaolin. Jilin J Chin Med 2020;40(8):3.

Zheng JH, Chen X, Huang FJ, Li LJ, Xu XM, Lei Y, Zhu XD, Tong XL. Data Mining of Medication Law of the Medical Cases of the Constraint Heat Stage of Pidan: Based on the Book New Discussion on Pi-dan-Understanding and Treatment of Metabolic Syndrome in Traditional Chinese Medicine. J Trad Chin Med 2021;62(9):9.

Régnier M, Rastelli M, Morissette A, Suriano F, Le Roy T, Pilon G, Delzenne NM, Marette A, Van Hul M, Cani PD. Rhubarb Supplementation Prevents Diet-Induced Obesity and Diabetes in Association with Increased Akkermansia muciniphila in Mice. Nutrients 2020;12(10):2932. DOI

Tramontin NDS, Luciano TF, Marques SO, De Souza CT, Muller AP. Ginger and avocado as nutraceuticals for obesity and its comorbidities. Phytother Res 2020;34(6):1282-90. DOI

Kim YJ, Shin YO, Ha YW, Lee S, Oh JK, Kim YS. Anti-obesity effect of Pinellia ternata extract in Zucker rats. Biol Pharm Bull 2006;29(6):1278-81. DOI

Lee JS, Kim KJ, Kim YH, Kim DB, Shin GH, Cho JH, Kim BK, Lee BY, Lee OH. Codonopsis lanceolata extract prevents diet-induced obesity in C57BL/6 mice. Nutrients 2014;6(11):4663-77. DOI

Wang S, Xu Z, Cai B, Chen Q. Berberine as a Potential Multi-Target Agent for Metabolic Diseases: A Review of Investigations for Berberine. Endocr Metab Immune Disord Drug Targets 2021;21(6):971-9. DOI

Dai J, Liang K, Zhao S, Jia W, Liu Y, Wu H, Lv J, Cao C, Chen T, Zhuang S, Hou X, Zhou S, Zhang X, Chen XW, Huang Y, Xiao RP, Wang YL, Luo T, Xiao J, Wang C. Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis. Proc Natl Acad Sci U S A 2018;115(26):E5896-E905. DOI

Dehghani S, Mehri S, Hosseinzadeh H. The effects of Crataegus pinnatifida (Chinese hawthorn) on metabolic syndrome: A review. Iran J Basic Med Sci 2019;22(5):460-8.

Kim D, Ku S. Beneficial Effects of Monascus sp. KCCM 10093 Pigments and Derivatives: A Mini Review. Molecules 2018;23(1):98. DOI

Gao J, Li W, Niu L, Cao R, Yin W. Isolation and structural elucidation of novel antimicrobial compounds from maggots of Chrysomyis megacephala Fabricius. Nat Prod Res 2015;29(3):239-46. DOI

Li QQ, Huo YY, Chen CJ, Zeng ZY, Xu FR, Cheng YX, Dong X. Biological Activities of Two Essential Oils from Pogostemon cablin and Eupatorium fortunei and Their Major Components against Fungi Isolated from Panax notoginseng. Chem Biodivers 2020;17(12):e2000520. DOI

Li R, Zhuang A, Ma J, Ji L, Hou X, Chen H, Pan X, Liu W. Effect of Jieduquyuziyin prescription-treated rat serum on MeCP2 gene expression in Jurkat T cells. In Vitro Cell Dev Biol Anim 2018;54(10):692-704. DOI

Morgan-Bathke M, Chen L, Oberschneider E, Harteneck D, Jensen MD. Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity. Am J Physiol Endocrinol Metab 2015;308(9):E830-46. DOI

Pan S, Cui Y, Fu Z, Zhang L, Xing H. MicroRNA-128 is involved in dexamethasone-induced lipid accumulation via repressing SIRT1 expression in cultured pig preadipocytes. J Steroid Biochem Mol Biol 2019;186:185-95. DOI

Shin SS, Yoon M. Regulation of Obesity by Antiangiogenic Herbal Medicines. Molecules 2020;25(19):4549. DOI

Zhang J, Kang H, Wang L, Zhao X. Chrysophanol ameliorates high-fat diet-induced obesity and inflammation in neonatal rats. Pharmazie 2018;73(4):228-33.

Chen L, Dong L, Zheng Z, Li M, Zhao Y, Duan J, Pan L, Tong XL. Effects of "Xiaogao Zhuanzhuo Decoction"on Lipid Peroxidation and Insulin Resistance in Rats of Obese Non-alcoholic Fatty Liver(in Chinese). Acta Universitatis Traditionis Medicalis Sinensis Pharmacologiaeque Shanghai 2011;25(6):58-62.

Lee HS, Lim SM, Jung JI, Kim SM, Lee JK, Kim YH, Cha KM, Oh TK, Moon JM, Kim TY, Kim EJ. Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1. Nutrients 2019;11(10):2475. DOI

Boughanem H, Cabrera-Mulero A, Millán-Gómez M, Garrido-Sánchez L, Cardona F, Tinahones FJ, Moreno-Santos I, Macías-González M. Transcriptional Analysis of FOXO1, C/EBP-α and PPAR-γ2 Genes and Their Association with Obesity-Related Insulin Resistance. Genes (Basel) 2019;10(9):706. DOI

Lee JE, Schmidt H, Lai B, Ge K. Transcriptional and Epigenomic Regulation of Adipogenesis. Mol Cell Biol 2019;39(11):e00601-18. DOI

Wafer R, Tandon P, Minchin JEN. The Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARG) in Adipogenesis: Applying Knowledge from the Fish Aquaculture Industry to Biomedical Research. Front Endocrinol (Lausanne) 2017;8:102. DOI

Janani C, Ranjitha Kumari BD. PPAR gamma gene-a review. Diabetes Metab Syndr 2015;9(1):46-50. DOI

Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 2004;86(11):839-48. DOI

Zhou JP, Ren YD, Xu QY, Song Y, Zhou F, Chen MY, Liu JJ, Chen LG, Pan JS. Obesity-Induced Upregulation of ZBTB7A Promotes Lipid Accumulation through SREBP1. Biomed Res Int 2020;2020:4087928. DOI