Selenium‑enriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway

Zhou,Xihong; Wang,Fengqin; Yang,Hangxian; Chen,Jingqing; Ren,Yang; Yuan,Zhangqin; Wang,Xinxia; Wang,Yizhen

doi:10.3892/mmr.2013.1859

Selenium‑enriched exopolysaccharides produced by Enterobacter cloacae Z0206 alleviate adipose inflammation in diabetic KKAy mice through the AMPK/SirT1 pathway

Authors:
- Xihong Zhou
- Fengqin Wang
- Hangxian Yang
- Jingqing Chen
- Yang Ren
- Zhangqin Yuan
- Xinxia Wang
- Yizhen Wang
View Affiliations

Affiliations: Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture, Zhejiang Provincial Laboratory of Feed and Animal Nutrition, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China
Published online on: December 11, 2013 https://doi.org/10.3892/mmr.2013.1859
Pages: 683-688

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

Polysaccharides belong to a structurally diverse class of macromolecules, with the necessary flexibility for the precise regulatory mechanisms and high capacity for carrying biological information. On the basis of a previous study regarding the administration of selenium‑enriched exopolysaccharides (Se‑ECZ‑EPS) produced by Enterobacter cloacae (E. cloacae) Z0206 which resulted in a reduction of blood glucose levels and showed significant anti‑inflammatory and anti‑diabetic effects, the present study was conducted to evaluate the effects and mechanism of EPS on the alleviation of fat inflammation in high‑fat‑diet (HFD) induced‑diabetic KKAy mice. The HFD induced‑diabetic KKAy mice were gavaged once daily with EPS (0.2 mg/g body weight) or distilled water, while the C57BL/6J mice were gavaged with distilled water. Six weeks later visceral adipose tissue (VAT) was collected for quantified polymerase chain reaction (qPCR) and western blot (WB) analysis. The results showed that following supplementation with EPS, interleukin (IL) 6, IL1β and tumor necrosis factor (TNF) α mRNA expression in VAT were significantly reduced, while Glut4, pAMPK and SirT1 protein expression were markedly increased when compared with KKAy mice gavaged with water. Furthermore, ATGL and HSL mRNA were also significantly decreased. Subsequently, 3T3‑L1 adipocytes were treated with insulin to induce insulin resistance to determine the mechanism by which EPS affects inflammation. Following the treatment of adipocytes with 100 nM insulin for 8 h, IL6 and TNFα mRNA expression were significantly increased, while the content of glucose uptake and Glut4 protein expression were significantly decreased. When treated with 100 nM insulin and 0.1 mg/ml EPS, no significant change in IL6 and TNFα mRNA expression or glucose uptake were observed. However, when SirT1‑siRNA or AMPKα1‑siRNA was tranfected into the 3T3‑L1 adipocytes prior to treatment with insulin and EPS, there was a significant increase in IL6 and TNFα mRNA abundance. In conclusion, VAT inflammation and lipolysis in HFD‑induced KKAy mice were significantly decreased following EPS usage. Moreover, EPS may alleviate VAT inflammation primarily through the AMPK/SirT1 pathway.

View Figures

View References

1	Wisse BE: The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 15:2792–2800. 2004. View Article : Google Scholar : PubMed/NCBI
2	Shoelson SE, Herrero L and Naaz A: Obesity, inflammation, and insulin resistance. Gastroenterology. 132:2169–2180. 2007. View Article : Google Scholar : PubMed/NCBI
3	Samaras K, Botelho NK, Chisholm DJ and Lord RV: Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring). 18:884–889. 2010. View Article : Google Scholar : PubMed/NCBI
4	Ooi VE and Liu F: Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem. 7:715–729. 2000. View Article : Google Scholar : PubMed/NCBI
5	Na HS, Lim YJ, Yun YS, Kweon MN and Lee HC: Ginsan enhances humoral antibody response to orally delivered antigen. Immune Netw. 10:5–14. 2010. View Article : Google Scholar : PubMed/NCBI
6	Ni W, Zhang X, Wang B, Chen Y, Han H, Fan Y, Zhou Y and Tai G: Antitumor activities and immunomodulatory effects of ginseng neutral polysaccharides in combination with 5-fluorouracil. J Med Food. 13:270–277. 2010. View Article : Google Scholar : PubMed/NCBI
7	Ananthi S, Raghavendran HR, Sunil AG, Gayathri V, Ramakrishnan G and Vasanthi HR: In vitro antioxidant and in vivo anti-inflammatory potential of crude polysaccharide from Turbinaria ornata (Marine Brown Alga). Food Chem Toxicol. 48:187–192. 2010. View Article : Google Scholar : PubMed/NCBI
8	Fu J, Fu J, Yuan J, Zhang N, Gao B, Fu G, Tu Y and Zhang Y: Anti-diabetic activities of Acanthopanax senticosus polysaccharide (ASP) in combination with metformin. Int J Biol Macromol. 50:619–623. 2012.PubMed/NCBI
9	Kaur R and Sandhu HS: In vivo changes in antioxidant system and protective role of selenium in chlorpyrifos-induced subchronic toxicity in bubalus bubalis. Environ Toxicol Pharmacol. 26:45–48. 2008. View Article : Google Scholar : PubMed/NCBI
10	Douillet C, Tabib A, Bost M, Accominotti M, Borson-Chazot F and Ciavatti M: A selenium supplement associated or not with vitamin E delays early renal lesions in experimental diabetes in rats. Proc Soc Exp Biol Med. 211:323–331. 1996. View Article : Google Scholar : PubMed/NCBI
11	Wang F, Yang H and Wang Y: Structure characterization of a fucose-containing exopolysaccharide produced by Enterobacter cloacae Z0206. Carbohydr Polym. 92:503–509. 2013. View Article : Google Scholar : PubMed/NCBI
12	Jin M, Lu Z, Huang M and Wang Y and Wang Y: Effects of Se-enriched polysaccharides produced by Enterobacter cloacae Z0206 on alloxan-induced diabetic mice. Int J Biol Macromol. 50:348–352. 2012. View Article : Google Scholar : PubMed/NCBI
13	Lu Z, Jin M, Huang M and Wang Y and Wang Y: Bioactivity of selenium-enriched exopolysaccharides produced by Enterobacter cloacae Z0206 in broilers. Carbohydr Polym. 96:131–136. 2013. View Article : Google Scholar : PubMed/NCBI
14	Xu CL, Wang YZ, Jin ML and Yang XQ: Preparation, characterization and immunomodulatory activity of selenium-enriched exopolysaccharide produced by bacterium Enterobacter cloacae Z0206. Bioresour Technol. 100:2095–2097. 2009. View Article : Google Scholar : PubMed/NCBI
15	Rigas DA and Osgood EE: Purification and properties of the phytohemagglutinin of Phaseolus vulgaris. J Biol Chem. 212:607–615. 1955.PubMed/NCBI
16	Fasshauer M, Klein J, Lossner U and Paschke R: Interleukin (IL)-6 mRNA expression is stimulated by insulin, isoproterenol, tumour necrosis factor alpha, growth hormone, and IL-6 in 3T3-L1 adipocytes. Horm Metab Res. 35:147–152. 2003. View Article : Google Scholar : PubMed/NCBI
17	Yoshioka K, Takahashi H, Homma T, Saito M, Oh KB, Nemoto Y and Matsuoka H: A novel fluorescent derivative of glucose applicable to the assessment of glucose uptake activity of Escherichia coli. Biochim Biophys Acta. 1289:5–9. 1996. View Article : Google Scholar
18	Ball SW, Bailey JR, Stewart JM, Vogels CM and Westcott SA: A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes. Can J Physiol Pharmacol. 80:205–209. 2002. View Article : Google Scholar : PubMed/NCBI
19	Zou C, Wang Y and Shen Z: 2-NBDG as a fluorescent indicator for direct glucose uptake measurement. J Biochem Biophys Methods. 64:207–215. 2005. View Article : Google Scholar : PubMed/NCBI
20	Dandona P, Aljada A and Bandyopadhyay A: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 25:4–7. 2004. View Article : Google Scholar : PubMed/NCBI
21	Jin M, Lu Z, Huang M and Wang Y and Wang Y: Sulfated modification and antioxidant activity of exopolysaccahrides produced by Enterobacter cloacae Z0206. Int J Biol Macromol. 48:607–612. 2011. View Article : Google Scholar : PubMed/NCBI
22	Bijland S, Mancini SJ and Salt IP: Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin Sci (Lond). 124:491–507. 2013. View Article : Google Scholar : PubMed/NCBI
23	Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A and Giugliano D: Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 106:2067–2072. 2002. View Article : Google Scholar : PubMed/NCBI
24	Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H and Dandona P: Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab. 85:2970–2973. 2000. 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	Zhang W, Zhang X, Wang H, Guo X, Li H, Wang Y, Xu X, Tan L, Mashek MT, Zhang C, Chen Y, Mashek DG, Foretz M, Zhu C, Zhou H, Liu X, Viollet B, Wu C and Huo Y: AMP-activated protein kinase α1 protects against diet-induced insulin resistance and obesity. Diabetes. 61:3114–3125. 2012.
27	Fontana L, Eagon JC, Trujillo ME, Scherer PE and Klein S: Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 56:1010–1013. 2007. View Article : Google Scholar : PubMed/NCBI
28	Winkler G, Kiss S, Keszthelyi L, Sápi Z, Ory I, Salamon F, Kovács M, Vargha P, Szekeres O, Speer G, Karádi I, Sikter M, Kaszás E, Dworak O, Gerö G and Cseh K: Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level. Eur J Endocrinol. 149:129–135. 2003.
29	Groop LC, Saloranta C, Shank M, Bonadonna RC, Ferrannini E and DeFronzo RA: The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 72:96–107. 1991. View Article : Google Scholar : PubMed/NCBI
30	Ravussin E and Smith SR: Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus. Ann N Y Acad Sci. 967:363–378. 2002. View Article : Google Scholar : PubMed/NCBI
31	Rajala MW and Scherer PE: Minireview: the adipocyte - at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 144:3765–3773. 2003. View Article : Google Scholar : PubMed/NCBI
32	Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, Minnemann T, Shulman GI and Kahn BB: Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 409:729–733. 2001. View Article : Google Scholar : PubMed/NCBI
33	Cantó C and Auwerx J: PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 20:98–105. 2009.PubMed/NCBI
34	Salt IP and Palmer TM: Exploiting the anti-inflammatory effects of AMP-activated protein kinase activation. Expert Opin Investig Drugs. 21:1155–1167. 2012. View Article : Google Scholar : PubMed/NCBI
35	Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA and Mayo MW: Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369–2380. 2004. View Article : Google Scholar : PubMed/NCBI
36	Ghosh HS, Spencer JV, Ng B, McBurney MW and Robbins PD: Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription. Biochem J. 408:105–111. 2007. View Article : Google Scholar : PubMed/NCBI
37	Yang Z, Kahn BB, Shi H and Xue BZ: Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1. J Biol Chem. 285:19051–19059. 2010. View Article : Google Scholar : PubMed/NCBI
38	Salminen A, Hyttinen JM and Kaarniranta K: AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl). 89:667–676. 2011.
39	Lihn AS, Pedersen SB, Lund S and Richelsen B: The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells. Mol Cell Endocrinol. 292:36–41. 2008. View Article : Google Scholar : PubMed/NCBI
40	Lihn AS, Jessen N, Pedersen SB, Lund S and Richelsen B: AICAR stimulates adiponectin and inhibits cytokines in adipose tissue. Biochem Biophys Res Commun. 316:853–858. 2004. View Article : Google Scholar : PubMed/NCBI
41	Gillum MP, Kotas ME, Erion DM, Kursawe R, Chatterjee P, Nead KT, Muise ES, Hsiao JJ, Frederick DW, Yonemitsu S, Banks AS, Qiang L, Bhanot S, Olefsky JM, Sears DD, Caprio S and Shulman GI: SirT1 regulates adipose tissue inflammation. Diabetes. 60:3235–3245. 2011. View Article : Google Scholar : PubMed/NCBI
42	Zhang M, Cui SW, Cheung PCK and Wang Q: Antitumor polysaccharides from mushrooms: a review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci Tech. 12:4–19. 2008.