Adiponectin promotes preadipocyte differentiation via the PPARγ pathway

Yang,Wenkai; Yang,Chunli; Luo,Jun; Wei,Yutao; Wang,Wenying; Zhong,Yingmei

doi:10.3892/mmr.2017.7881

Adiponectin promotes preadipocyte differentiation via the PPARγ pathway

Authors:
- Wenkai Yang
- Chunli Yang
- Jun Luo
- Yutao Wei
- Wenying Wang
- Yingmei Zhong
View Affiliations

Affiliations: Department of Cardio‑Thoracic Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi 341000, P.R. China, Department of Intensive Care, Jiangxi People's Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Cardio‑Thoracic Surgery, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, Xinjiang 832008, P.R. China
Published online on: October 26, 2017 https://doi.org/10.3892/mmr.2017.7881
Pages: 428-435

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

According to the results of a preliminary study, it was hypothesized that the effects of adiponectin (APN) on the improvement of atherosclerosis may be associated with adipocyte differentiation and peroxisome proliferator‑activated receptor γ (PPARγ). The present study simulated the inflammatory environment of epicardial adipose tissue by stimulating mature adipocytes with lipopolysaccharide (LPS); subsequently, the differentiation of 3T3‑L1 preadipocytes was observed. 3T3‑L1 preadipocytes were infected with an adenovirus containing the human adiponectin gene apM1 (Ad‑apM1) and were co‑cultured with mature adipocytes stimulated with LPS. Differentiation into mature adipocytes was initiated using differentiation medium. After 8 days, an MTT assay was used to examine cell viability and oil red O staining was used to observe preadipocyte differentiation. In addition, the mRNA expression levels of monocyte chemoattractant protein‑1 (MCP‑1), interleukin (IL)‑6, IL‑8 and tumor necrosis factor α (TNF‑α) were examined by quantitative polymerase chain reaction, and the protein expression levels of PPARγ, CCAAT/enhancer binding protein α (C/EBPα) and preadipocyte factor‑1 (Pref‑1) were measured by western blotting. The results indicated that APN overexpression significantly increased preadipocyte differentiation and cell viability, inhibited MCP‑1, IL‑6, IL‑8 and TNF‑α expression, upregulated PPARγ and C/EBPα expression, and downregulated Pref‑1 under LPS stimulation. In addition, inhibition of PPARγ activity by T0070907 markedly attenuated the effects of APN overexpression. Taken together, the present study demonstrated that the effects of APN on the promotion of preadipocyte differentiation under inflammatory conditions may involve the PPARγ signaling pathway, and at least partly depends on upregulation of PPARγ expression.

View Figures

View References

1	Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z, Dong NG and Chen XZ: Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol. 10:22011. View Article : Google Scholar : PubMed/NCBI
2	Barton M: Obesity and aging: Determinants of endothelial cell dysfunction and atherosclerosis. Pflugers Arch. 460:825–837. 2010. View Article : Google Scholar : PubMed/NCBI
3	Ragbir S and Farmer JA: Dysfunctional high-density lipoprotein and atherosclerosis. Curr Atheroscler Rep. 12:343–348. 2010. View Article : Google Scholar : PubMed/NCBI
4	Caccamo G, Bonura F, Bonura F, Vitale G, Novo G, Evola S, Evola G, Grisanti MR and Novo S: Insulin resistance and acute coronary syndrome. Atherosclerosis. 211:672–675. 2010. View Article : Google Scholar : PubMed/NCBI
5	Ridker PM and Silvertown JD: Inflammation, C-reactive protein, and atherothrombosis. J Periodontol. 79:1544–1551. 2008. View Article : Google Scholar : PubMed/NCBI
6	Stamatelopoulos KS, Kitas GD, Papamichael CM, Chryssohoou E, Kyrkou K, Georgiopoulos G, Protogerou A, Panoulas VF, Sandoo A, Tentolouris N, et al: Atherosclerosis in rheumatoid arthritis versus diabetes: A comparative study. Arterioscler Thromb Vasc Biol. 29:1702–1708. 2009. View Article : Google Scholar : PubMed/NCBI
7	Iacobellis G, Corradi D and Sharma AM: Epicardial adipose tissue: Anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med. 2:536–543. 2005. View Article : Google Scholar : PubMed/NCBI
8	Ruisi P, Makaryus JN, Ruisi M and Makaryus AN: Inflammatory bowel disease as a risk factor for premature coronary artery disease. J Clin Med Res. 7:257–261. 2015. View Article : Google Scholar : PubMed/NCBI
9	Carneiro FS, Webb RC and Tostes RC: Emerging role for TNF-α in erectile dysfunction. J Sex Med. 7:3823–3834. 2010. View Article : Google Scholar : PubMed/NCBI
10	Saarikoski LA, Juonala M, Huupponen R, Viikari JS, Lehtimäki T, Jokinen E, Hutri-Kähönen N, Taittonen L, Laitinen T and Raitakari OT: Low serum adiponectin levels in childhood and adolescence predict increased intima-media thickness in adulthood. The cardiovascular risk in young finns study. Ann Med. 49:42–50. 2017. View Article : Google Scholar : PubMed/NCBI
11	Gasbarrino K, Gorgui J, Nauche B, Côté R and Daskalopoulou SS: Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis. Metabolism. 65:968–986. 2016. View Article : Google Scholar : PubMed/NCBI
12	Liu X, Malki A, Cao Y, Li Y, Qian Y, Wang X and Chen X: Glucose-and triglyceride-lowering dietary penta-o-galloyl-α-d-glucose reduces expression of PPARγ and C/EBPα, induces p21-mediated G1 phase cell cycle arrest and inhibits adipogenesis in 3T3-L1 preadipocytes. Exp Clin Endocrinol Diabetes. 123:308–316. 2015. View Article : Google Scholar : PubMed/NCBI
13	Lv S, Wu L, Cheng P, Yu J, Zhang A, Zha J, Liu J, Wang L, DI W, Hu M, et al: Correlation of obesity and osteoporosis: Effect of free fatty acids on bone marrow-derived mesenchymal stem cell differentiation. Exp Ther Med. 1:603–610. 2010. View Article : Google Scholar : PubMed/NCBI
14	Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, et al: Visfatin: A protein secreted by visceral fat that mimics the effects of insulin. Science. 307:426–430. 2005. View Article : Google Scholar : PubMed/NCBI
15	Jensen MD: Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 93 11 Suppl 1:S57–S63. 2008. View Article : Google Scholar : PubMed/NCBI
16	Antuna-Puente B, Feve B, Fellahi S and Bastard JP: Adipokines: The missing link between insulin resistance and obesity. Diabetes Metab. 34:2–11. 2008. View Article : Google Scholar : PubMed/NCBI
17	Dubuisson O, Dhurandhar EJ, Krishnapuram R, Kirk-Ballard H, Gupta AK, Hegde V, Floyd E, Gimble JM and Dhurandhar NV: PPARgamma-independent increase in glucose uptake and adiponectin abundance in fat cells. Endocrinology. 152:3648–3660. 2011. View Article : Google Scholar : PubMed/NCBI
18	Chen X, Luo Y, Huang Z, Jia G, Liu G and Zhao H: Role of phosphotyrosine interaction domain containing 1 in porcine intramuscular preadipocyte proliferation and differentiation. Anim Biotechnol. 27:287–294. 2016. View Article : Google Scholar : PubMed/NCBI
19	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. View Article : Google Scholar : PubMed/NCBI
20	Chen C, He H, Luo Y, Zhou M, Yin D and He M: Involvement of Bcl-2 signal pathway in the protective effects of apigenin on anoxia/reoxygenation-induced myocardium injury. J Cardiovasc Pharmacol. 67:152–163. 2016. View Article : Google Scholar : PubMed/NCBI
21	Guo W, Li Y, Liang W, Wong S, Apovian C, Kirkland JL and Corkey BE: Beta-mecaptoethanol suppresses inflammation and induces adipogenic differentiation in 3T3-F442A murine preadipocytes. PLoS One. 7:e409582012. View Article : Google Scholar : PubMed/NCBI
22	Zhang H, Huang Y, Bu D, Chen S, Tang C, Wang G, Du J and Jin H: Endogenous sulfur dioxide is a novel adipocyte-derived inflammatory inhibitor. Sci Rep. 6:270262016. View Article : Google Scholar : PubMed/NCBI
23	Lu JC, Chang YT, Wang CT, Lin YC, Lin CK and Wu ZS: Trichostatin A modulates thiazolidinedione-mediated suppression of tumor necrosis factor α-induced lipolysis in 3T3-L1 adipocytes. PLoS One. 8:e715172013. View Article : Google Scholar : PubMed/NCBI
24	Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, Sarov-Blat L, O'Brien S, Keiper EA, Johnson AG, et al: Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 108:2460–2466. 2003. View Article : Google Scholar : PubMed/NCBI
25	Glass CK and Olefsky JM: Inflammation and lipid signaling in the etiology of insulin resistance. Cell Metab. 15:635–645. 2012. View Article : Google Scholar : PubMed/NCBI
26	Scherer PE, Williams S, Fogliano M, Baldini G and Lodish HF: A novel serum-protein similar to C1Q, produced exclusively in adipocytes. J Biol Chem. 270:26746–26749. 1995. View Article : Google Scholar : PubMed/NCBI
27	Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y and Matsubara K: CDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (Adipose most abundant gene transcript 1). Biochem Biophys Res Commun. 221:286–289. 1996. View Article : Google Scholar : PubMed/NCBI
28	Fu YC, Luo NL, Klein RL and Garvey WT: Adiponectin promotes adipocyte differentiation, insulin sensitivity and lipid accumulation. J Lipid Res. 46:1369–1379. 2005. View Article : Google Scholar : PubMed/NCBI
29	Bauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, Penicaud L, Maeda N, Funahashi T and Brichard SM: Overexpression of adiponectin targeted to adipose tissue in transgenic mice: Impaired adipocyte differentiation. Endocrinology. 148:1539–1549. 2007. View Article : Google Scholar : PubMed/NCBI
30	Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y and Matsuzawa Y: Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 96:1723–1732. 2000.PubMed/NCBI
31	Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, et al: Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class a scavenger receptor expression in human monocyte-derived macrophages. Circulation. 103:1057–1063. 2001. View Article : Google Scholar : PubMed/NCBI
32	Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, et al: Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation. 109:2046–2049. 2004. View Article : Google Scholar : PubMed/NCBI
33	Ajuwon KM and Spurlock ME: Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol. 288:R1220–R1225. 2005. View Article : Google Scholar : PubMed/NCBI
34	Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, et al: Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 102:1296–1301. 2000. View Article : Google Scholar : PubMed/NCBI
35	Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA and Spurlock ME: Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun. 316:924–929. 2004. View Article : Google Scholar : PubMed/NCBI
36	Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A and Richelsen B: Regulation of adiponectin by adipose tissue-derived cytokines: In vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab. 285:E527–E533. 2003. View Article : Google Scholar : PubMed/NCBI
37	Kern PA, Di Gregorio GB, Lu T, Rassouli N and Ranganathan G: Adiponectin expression from human adipose tissue: Relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 52:1779–1785. 2003. View Article : Google Scholar : PubMed/NCBI
38	Farmer SR: Transcriptional control of adipocyte formation. Cell Metab. 4:263–273. 2006. View Article : Google Scholar : PubMed/NCBI
39	Evans RM, Barish GD and Wang YX: PPARs and the complex journey to obesity. Nat Med. 10:355–361. 2004. View Article : Google Scholar : PubMed/NCBI
40	Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, Koder A and Evans RM: PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell. 4:585–595. 1999. View Article : Google Scholar : PubMed/NCBI
41	Kolehmainen M, Uusitupa MI, Alhava E, Laakso M and Vidal H: Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue of massively obese subjects. J Clin Endocrinol Metab. 88:1717–1722. 2003. View Article : Google Scholar : PubMed/NCBI
42	Tontonoz P and Spiegelman BM: Fat and beyond: The diverse biology of PPARgamma. Annu Rev Biochem. 77:289–312. 2008. View Article : Google Scholar : PubMed/NCBI
43	Zhang J, Fu M, Cui T, Xiong C, Xu K, Zhong W, Xiao Y, Floyd D, Liang J, Li E, et al: Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity. Proc Natl Acad Sci USA. 101:10703–10708. 2004. View Article : Google Scholar : PubMed/NCBI
44	Rosen ED and MacDougald OA: Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 7:885–896. 2006. View Article : Google Scholar : PubMed/NCBI
45	An Z, Muthusami S, Yu JR and Park WY: T0070907, a PPAR γ inhibitor, induced G2/M arrest enhances the effect of radiation in human cervical cancer cells through mitotic catastrophe. Reprod Sci. 21:1352–1361. 2014. View Article : Google Scholar : PubMed/NCBI
46	Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ and Spiegelman BM: C/EBPalpha induces adipogenesis through PPARgamma: A unified pathway. Genes Dev. 16:22–26. 2002. View Article : Google Scholar : PubMed/NCBI
47	Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, Stoeckert CJ Jr, Liu XS and Lazar MA: PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 22:2941–2952. 2008. View Article : Google Scholar : PubMed/NCBI
48	Smas CM, Chen L and Sul HS: Cleavage of membrane-associated pref-1 generates a soluble inhibitor of adipocyte differentiation. Mol Cell Biol. 17:977–988. 1997. View Article : Google Scholar : PubMed/NCBI
49	Nawrocki AR, Hofmann SM, Teupser D, Basford JE, Durand JL, Jelicks LA, Woo CW, Kuriakose G, Factor SM, Tanowitz HB, et al: Lack of association between adiponectin levels and atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 30:1159–1165. 2010. View Article : Google Scholar : PubMed/NCBI