Open Access

Expression of apolipoprotein M and its association with adiponectin in an obese mouse model

  • Authors:
    • Liu Yang
    • Tie Li
    • Shuiping Zhao
    • Saidan Zhang
  • View Affiliations

  • Published online on: July 9, 2019     https://doi.org/10.3892/etm.2019.7755
  • Pages: 1685-1692
  • Copyright: © Yang 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: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The aim of the present study was to explore the association between apolipoprotein M (ApoM) and adiponectin, and the underlying mechanism, via observation of ApoM expression in an obese mouse model. For in vivo experiments, mice were randomly distributed into four groups: Control group, obese group, obese group treated with adiponectin, and normal group treated with adiponectin. Body weight, plasma adiponectin, blood glucose and fasting insulin were measured and visceral adipose tissue was weighed at the end of the experiment. ApoM and transcription factor forkhead box A2 (Foxa2) mRNA expression in the mouse liver was evaluated and the protein level of ApoM detected. For in vitro experiments, an insulin‑resistant (IR) hepatic cell model was established by inducing the HepG2 cell line with a high concentration of insulin. Following treatment with adiponectin, changes in ApoM and Foxa2 mRNA expression and ApoM protein expression were evaluated in the control and IR HepG2 cells. Results demonstrated that compared with the control group, body weight, visceral adipose tissue weight, blood glucose, fasting insulin and insulin‑resistance index (HOMA‑IR) were significantly increased in the obese group, whilst plasma adiponectin, ApoM mRNA expression, Foxa2 mRNA expression and ApoM protein in the mouse liver were all significantly decreased. Following intervention with adiponectin in obese mice, blood glucose, insulin and HOMA‑IR were significantly decreased, whilst plasma adiponectin, ApoM mRNA expression, Foxa2 mRNA expression and ApoM protein were all significantly increased. However, no significant difference was observed in visceral adipose tissue weight following the intervention of adiponectin in obese mice. In vitro, in the absence of intervention, ApoM and Foxa2 mRNA expression and ApoM protein expression were significantly lower in IR HepG2 cells compared with HepG2 cells. Following intervention with adiponectin on IR HepG2 cells, ApoM and Foxa2 mRNA expression and ApoM protein expression were significantly increased. However, the intervention did not have any effect on HepG2 cells. In conclusion, intervention with adiponectin elevated ApoM mRNA expression, potentially via relieving IR and upregulating Foxa2 mRNA expression.

References

1 

Ravussin A and Bouchard C: Human genomics and obesity: Finding appropriate drug targets. Eur J Pharmacol. 410:131–145. 2000. View Article : Google Scholar : PubMed/NCBI

2 

Abbasi F, Brown BW Jr, Lamendola C, McLaughlin T and Reaven GM: Relationship between obesity, insulin resistance, and coronary heart disease risk. J Am Coll Cardiol. 40:937–943. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Sacks FM; Expert Group on HDL Cholesterol, : The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: Expert group recommendations. AM J cardiol. 90:139–143. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Wolfrum C, Poy MN and Stoffel M: Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med. 11:418–422. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Everson SA, Goldbeng DE, Helmrich SP, Lakka TA, Lynch JW, Kaplan GA and Salonen JT: Weight gain and the risk of developing insulin resistance syndrome. Diabetes Care. 21:1637–1643. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Caro JF: Clinical review 26: Insulin resistance in obese and nonobese man. J Clin Endocrinol Metab. 73:691–695. 1991. View Article : Google Scholar : PubMed/NCBI

7 

Podskalny JM, Takeda S, Silverman RE, Tran D, Carpentier JL, Orci L and Gorden P: Insulin receptors and bioresponses in a human liver cell line (Hep G-2). Eur J Biochem. 1502:401–407. 1985. View Article : Google Scholar

8 

Brillon DJ, Freidenberg GR, Henry RR and Olefsky JM: Mechanism of defective insulin-receptor kinase activity in NIDDM. Evidence for two receptor populations. Diabetes. 38:397–403. 1989. View Article : Google Scholar : PubMed/NCBI

9 

Hari J and Roth RA: Defective internalization of insulin and its receptor in cells expressing mutated insulin receptors lacking kinase activity. J Biol Chem. 262:15341–15344. 1987.PubMed/NCBI

10 

Amatruda JM and Roncone AM: Normal hepatic insulin receptor autophosphorylation in nonketotic diabetes mellitus. Biochem Biophys Res Commun. 129:163–170. 1985. View Article : Google Scholar : PubMed/NCBI

11 

Changgui L, Guang N and Jialun C: Establishing and identifing insulin resistant HepG2 cell line. Chin J Diabetes. 7:198–199. 1999.

12 

Xie P, Liu ML, Gu YP, Lu J, Xu X, Zeng WM and Song HP: Oestrogen improves glucose metabolism and insulin signal transduction in HepG2 cells. Clin Exp Pharmacol Physiol. 30:643–648. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Zhang HJ, Ji BP, Chen G, Zhou F, Luo YC, Yu HQ, Gao FY, Zhang ZP and Li HY: A combination of grape seed-derived procyanidins and gypenosides alleviates insulin resistance in mice and HepG2 cells. J Food Sci. 74:H1–H7. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Xie W, Wang W, Su H, Xing D, Pan Y and Du L: Effect of ethanolic extracts of Ananas comosus L. leaves on insulin sensitivity in rats and HepG2. Comp Biochem Physiol C Toxicol Pharmacol. 143:429–435. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Haluzik M, Parízková J and Haluzík MM: Adiponectin and its role in the obesity induced insulin resistance and related complications. Physiol Res. 53:123–129. 2004.PubMed/NCBI

16 

Yamashita R, Saito T, Satoh S, Kaburagi Y and Sekihara H: Effects of dehydroepiandrosterone on gluconeogenic enzymes and glucose uptake in human hepatoma cell line, HepG2. Endocr J. 52:727–733. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Chavez-Tapia NC, Rosso N and Tiribelli C: In vitro models for the study of non-alcoholic fatty liver disease. Curr Med Chem. 18:1079–1084. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Pullinger CR, North JD, Teng BB, Rifici VA, Ronhild de Brito AE and Scott J: The apolipoprotein B gene is constituently expressed in HepG2 cells: Regulation by oleic acid, albumin, and insulin, and measurement of the mRNA half life. J Lipid Res. 30:1065–1077. 1989.PubMed/NCBI

19 

Chao PM and Kuo YH, Lin YS, Chen CH, Chen SW and Kuo YH: The metabolic benefits of Polygonum hypoleucum Ohwi in HepG2 cells and Wistar rats under lipogenic stress. J Agric Food Chem. 58:5174–5180. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Liu Z, Kuang W, Xu X, Li D, Zhu W, Lan Z and Zhang X: Putative identification of components in Zengye Decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells. J Chromatogr B Analyt Technol Biomed Life Sci. 1073:145–153. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Zheng X, Ke Y, Feng A, Yuan P, Zhou J, Yu Y, Wang X and Feng W: The Mechnism by which amentoflavone improves insulin resistance in HepG2 cells. Molecules. 21(pii): E6242016. View Article : Google Scholar : PubMed/NCBI

22 

Nie J, Chang Y, Li Y, Zhou Y, Qin J, Sun Z and Li H: Caffeic acid phenethyl ester (Propolis Extract) ameliorates insulin resistance by inhibiting JNK and NF-κB inflammatory pathways in diabetic mice and HepG2 cell models. J Agric Food Chem. 65:9041–9053. 2017. View Article : Google Scholar : PubMed/NCBI

23 

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

24 

Horowitz BS, Goldberg IJ, Merab J, Vanni TM, Ramakrishnan R and Ginsberg HN: Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol. J Clin Invest. 91:1743–1752. 1993. View Article : Google Scholar : PubMed/NCBI

25 

Ruiz M, Frej C, Holmér A, Guo LJ, Tran S and Dahlbäck B: High-density lipoprotein-associated apolipoprotein M limits endothelial inflammation by delivering Sphingosine-1-phosphate to the Sphingosine-1-phosphate receptor 1. Arterioscler Thromb Vasc Biol. 37:118–129. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Ruiz M, Okada H and Dahlbäck B: HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium. Lipids Health Dis. 16:362017. View Article : Google Scholar : PubMed/NCBI

27 

Frej C, Mendez AJ, Ruiz M, Castillo M, Hughes TA, Dahlbäck B and Goldberg RB: A shift in ApoM/S1P between HDL-Particles in women with type 1 diabetes mellitus is associated with impaired anti-Inflammatory effects of the ApoM/S1P complex. Arterioscler Thromb Vasc Biol. 37:1194–1205. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Lee M, Kim JI, Choi S, Jang Y and Sorn SR: The effect of apoM polymorphism associated with HDL metabolism on obese Korean Adults. J Nutrigenet Nutrigenomics. 9:306–317. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Calabro P and Yeh ET: Obesity, inflammation, and vascular disease: The role of the adipose tissue as an endocrine organ. Subcell Biochem. 42:63–91. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Xu N, Nilsson-Ehle P, Hurtig M and Ahrén B: Both leptin and leptin-receptor are essential for apolipoprotein M expression in vivo. Biochem Biophys Res Commun. 321:916–921. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Luo G, Hurtig M, Zhang X, Nilsson-Ehle P and Xu N: Leptin inhibits apolipoprotein M transcription and secretion in human hepatoma cell line, HepG2 cells. Biochim Biophys Acta. 1734:198–202. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Tsubakio-Yamamoto K, Sugimoto T, Nishida M, Okano R, Monden Y, Kitazume-Taneike R, Yamashita T, Nakaoka H, Kawase R, Yuasa-Kawase M, et al: Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography. Metabolism. 61:1763–1770. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Altinova AE, Toruner F, Bukan N, Yasar DG, Akturk M, Cakir N and Arslan M: Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects. Endocr J. 54:221–226. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Zietz B, Herfaah H, Paul G, Ehling A, Müller-Ladner U, Schölmerich J and Schäffler A: Adiponectin represents and independent cardiovascular risk factor predicting serum HDL-C levels in type 2 diabetes. FEBS Lett. 545:103–104. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Dullaart RP, de Vries R, van Tol A and Sluiter WJ: Lower plasma adiponectin is a marker of increased intima-media thickness assiciated with type 2 diabetes mellitus and with male gender. Eur J Endocrinol. 156:387–394. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM and Kaestner KH: Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia. Genes Dev. 15:1706–1715. 2001. View Article : Google Scholar : PubMed/NCBI

37 

Lee CS, Friedman JR, Fulmer JT and Kaestner KH: The initiation of liver development is dependent on Foxa transcription factors. Nature. 435:944–947. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Wolfrum C, Howell JJ, Ndungo E and Stoffel M: Foxa2 activity increases plasma high density lipoprotein levels by regulating apolipoprotein M. J Biol Chem. 283:16940–16949. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

September 2019
Volume 18 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Yang, L., Li, T., Zhao, S., & Zhang, S. (2019). Expression of apolipoprotein M and its association with adiponectin in an obese mouse model. Experimental and Therapeutic Medicine, 18, 1685-1692. https://doi.org/10.3892/etm.2019.7755
MLA
Yang, L., Li, T., Zhao, S., Zhang, S."Expression of apolipoprotein M and its association with adiponectin in an obese mouse model". Experimental and Therapeutic Medicine 18.3 (2019): 1685-1692.
Chicago
Yang, L., Li, T., Zhao, S., Zhang, S."Expression of apolipoprotein M and its association with adiponectin in an obese mouse model". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1685-1692. https://doi.org/10.3892/etm.2019.7755