Browse > Article
http://dx.doi.org/10.5851/kosfa.2017.37.4.529

Lactobacillus acidophilus NS1 Reduces Phosphoenolpyruvate Carboxylase Expression by Regulating HNF4α Transcriptional Activity  

Park, Sung-Soo (Department of Biological Sciences, College of Science, Chonnam National University)
Yang, Garam (Department of Biological Sciences, College of Science, Chonnam National University)
Kim, Eungseok (Department of Biological Sciences, College of Science, Chonnam National University)
Publication Information
Food Science of Animal Resources / v.37, no.4, 2017 , pp. 529-534 More about this Journal
Abstract
Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that Lactobacillus acidophilus NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited $HNF4{\alpha}-induced$ PEPCK promoter activity in HepG2 cells without change of $HNF4{\alpha}$ mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating $HNF4{\alpha}$ transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.
Keywords
Lactobacillus acidophilus NS1; $HNF4{\alpha}$; PEPCK; gluconeogenesis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Jansen, M. S., Nagel, S. C., Miranda, P. J., Lobenhofer, E. K., Afshari, C. A., and McDonnell, D. P. (2004) Short-chain fatty acid enhances nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition. Proc. Natl. Acad. Sci. 101, 7199-7204.   DOI
2 Kahn, S. E., Hull, R. L., and Utzschneider, K. M. (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840-846.   DOI
3 Keipert, S. and Jastroch, M. (2014) Brite/beige fat and UCP1 - Is it thermogenesis? Biochim. Biophys. Acta 1837, 1075-1082.   DOI
4 Kvasnovsky, C. L., Bjarnason, I., and Papagrigoriadis, S. (2015) What colorectal surgeons should know about probiotics: A review. Colectal. Dis. 17, 840-848.   DOI
5 Liu, N. C., Lin, W. J., Kim, E. S., Collins, L. L., Lin, H. Y., Yu, I. C., Sparks, J. D., Chen, L. M., Lee, Y. F., and Chang, C. S. (2007) Loss of TR4 orphan nuclear receptor reduces phosphoenolpyruvate carboxykinase-mediated gluconeogenesis. Diabetes 56, 2901-2909.   DOI
6 Lu, H. (2016) Crosstalk of $HNF4{\alpha}$ with extracellular and intracellular signaling pathways in the regulation of hepatic metabolism of drugs and lipids. Acta Pharmaceutica Sinica B 6, 393-408.   DOI
7 Mazural, N., Broelz, E., Storr, M., and Enck, P. (2015) Probiotic therapy of the irritable bowel syndrome: Why is the evidence still poor and what can be done about it? J. Neurogastroenterol. Motil. 21, 471-485.   DOI
8 Musso, G., Gambino, R., and Cassader, M. (2010) Obesity, diabetes, and gut microbiota: The hygiene hypothesis expanded? Diabetes Care 33, 2277-2284.   DOI
9 Nagpal, R., Kumar, M., Yadav, A. K., Hemalatha, R., Yadav, H., Marotta, F., and Yamashiro, Y. (2016) Gut microbiota in health and disease: An overview focused on metabolic inflammation. Benef Microbs. 7, 181-194.   DOI
10 Song, K. H., Li, T., and Chiang, J. Y. L. (2006) A prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4 that regulates the cholesterol 7-hydroxylase gene. J. Biol. Chem. 281, 10081-10088.   DOI
11 Yamamoto, T., Shimano, H., Nakagawa, Y., Ide, T., Yahagi, N., Matsuzaka, T., Nakakuki, M., Takahashi, A., Suzuki, H., Sone, H., Toyoshima, H., Sato, R., and Yamada, N. (2004) SREBP-1 interacts with hepatocyte nuclear factor-4 and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes. J. Biol. Chem. 279, 12027-12035.   DOI
12 Stark, R., Guebre-Egziabher, F., Zhao, X., Feriod, C., Dong, J., Alves, T. C., Ioja, S., Pongratz, R. L., Bhanot, S., Roden, M., Cline, G. W., Shulman, G. I., and Kibbey, R. G. (2014) A role for mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) in the regulation of hepatic gluconeogenesis. J. Biol. Chem. 289, 7257-7263.   DOI
13 Stoffel, M. and Duncan, S. A. (1997) The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc. Natl. Acad. Sci. USA 94, 13209-13214.   DOI
14 Yamagata, K. (2014) Roles of $HNF1{\alpha}$ and $HNF4{\alpha}$ in pancreatic $\beta$-cells: Lessons from a monogenic form of diabetes (MODY). Vitamins and Hormones 95, 407-423.
15 Yang, J., Kalhan, S. C., and Hanson, R. W. (2009) What is the metabolic role of phosphoenolpyruvate carboxykinase. J. Biol. Chem. 284, 27025-27029.   DOI
16 You, H. J., Lee, S. H., and Ko, G. P. (2015) Concepts and strategies of the human intestinal microbiome research. Korean J. Public Health 52, 11-19.
17 Golozoubova, V., Hohtola, E., Matthias, A., Jacobsson, A., Cannon, B., and Nedergaard, J. (2001) Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. FASEB J. 15, 2048-2050.   DOI
18 Babeu, J. P. and Boudreau, F. (2014) Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J. Gastroenterol. 20, 22-30.   DOI
19 Cassuto, H., Kochan, K., Chakravarty, K., Cohen, H., Blum, B., Olswang, Y., Hakimi, P., Xu, C., Massillon, D., Hanson, R. W., and Reshef, L. (2005) Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate carboxykinase in the liver via an extended glucocorticoid regulatory unit. J. Biol. Chem. 280, 33873-33884.   DOI
20 Gerich, J. E., Meyer, C., Woerle, H. J., and Stumvoll, M. (2001) Renal gluconeogenesis: Its importance in human glucose homeostasis. Diabetes Care 24, 382-391.   DOI
21 Hemarajata P, Versalovic J. (2013) Effects of probiotics on gut microbiota: Mechanisms of intestinal immunomodulation and neuromodulation. Ther. Adv. Gastroenterol. 6, 39-51.   DOI