Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2017 Volume 16 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2017 Volume 16 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice

  • Authors:
    • Min Li
    • Antara Sharma
    • Chunyan Yin
    • Xinrui Tan
    • Yanfeng Xiao
  • View Affiliations / Copyright

    Affiliations: Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Pediatrics Department, 2nd Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 680-686
    |
    Published online on: May 26, 2017
       https://doi.org/10.3892/mmr.2017.6637
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed to investigate the effect of metformin on the induction of autophagy in the liver and adipose tissues of a mouse model of obesity. C57BL/6J mice were fed a high‑fat diet (HFD) for 12 weeks to induce obesity‑associated hepatic steatosis, and treated with metformin (150 mg/kg/d) by intraperitoneal injection for the final 4 weeks of HFD feeding. Body weight was recorded weekly, and the food intake of the mice was recorded daily during the treatment period. Liver and adipose tissues were harvested for histological and molecular analyses. The results revealed that metformin significantly reduced body weight without altering food intake in the HFD mice, particularly in the epididymal white adipose tissue (eWAT). Metformin treatment ameliorated HFD‑induced hepatic steatosis and serum levels of triglycerides, which was consistent with a marked increase in the expression levels of microtubule‑associated protein 1 light chain 3 (LC3) and AMP‑activated protein kinase (AMPK) in the liver following metformin treatment. However, metformin suppressed the expression of LC3 in the eWAT without altering the expression of AMPK, compared with that in the HFD mice. In conclusion, metformin reduced the body weight and hepatic steatosis of the HFD‑induced obese mice, without altering food intake. The effects of metformin treatment may be attributable to the improved induction of hepatic autophagy and the inhibited induction of adipose tissue autophagy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Ogden CL, Carroll MD, Kit BK and Flegal KM: Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA. 311:806–814. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Reed M, Cygan H, Lui K and Mullen M: Identification, prevention, and management of childhood overweight and obesity in a pediatric primary care center. Clin Pediatr (Phila). 55:860–866. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Deiuliis JA: MicroRNAs as regulators of metabolic disease: Pathophysiologic significance and emerging role as biomarkers and therapeutics. Int J Obes (Lond). 40:88–101. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Sweeting AN, Hocking SL and Markovic TP: Pharmacotherapy for the treatment of obesity. Mol Cell Endocrinol. 418:173–183. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Lee A and Morley JE: Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res. 6:47–53. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Kim HJ, Zhang XH, Park EY, Shin KH, Choi SH, Chun BG and Kim DH: Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice. Physiol Behav. 110–111:213–220. 2013. View Article : Google Scholar

7 

Woo SL, Xu H, Li H, Zhao Y, Hu X, Zhao J, Guo X, Guo T, Botchlett R, Qi T, et al: Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. PLoS One. 9:e911112014. View Article : Google Scholar : PubMed/NCBI

8 

Song YM, Lee YH, Kim JW, Ham DS, Kang ES, Cha BS, Lee HC and Lee BW: Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway. Autophagy. 11:46–59. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Lavallard VJ and Gual P: Autophagy and non-alcoholic fatty liver disease. Biomed Res Int. 2014:1201792014. View Article : Google Scholar : PubMed/NCBI

10 

Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, Green-Thompson ZW, Jimenez-Sanchez M, Korolchuk VI, Lichtenberg M, Luo S, et al: Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 90:1383–1435. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Lee JW, Park S, Takahashi Y and Wang HG: The association of AMPK with ULK1 regulates autophagy. PLoS One. 5:e153942010. View Article : Google Scholar : PubMed/NCBI

12 

Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM and Czaja MJ: Autophagy regulates lipid metabolism. Nature. 458:1131–1135. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kovsan J, Blüher M, Tarnovscki T, Klöting N, Kirshtein B, Madar L, Shai I, Golan R, Harman-Boehm I, Schön MR, et al: Altered autophagy in human adipose tissues in obesity. J Clin Endocrinol Metab. 96:E268–E277. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Singh R, Xiang Y, Wang Y, Baikati K, Cuervo AM, Luu YK, Tang Y, Pessin JE, Schwartz GJ and Czaja MJ: Autophagy regulates adipose mass and differentiation in mice. J Clin Invest. 119:3329–3339. 2009.PubMed/NCBI

15 

National Research Council (US) Committee for the update of the guide for the care and use of laboratory animals: Guide for the care and use of laboratory animals. 8th. Washington, DC: National Academies Press; 2011

16 

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

17 

Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M and Melchionda N: Metformin in non-alcoholic steatohepatitis. Lancet. 358:893–894. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M and Marchesini G: A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 100:1082–1090. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Shi WY, Xiao D, Wang L, Dong LH, Yan ZX, Shen ZX, Chen SJ, Chen Y and Zhao WL: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy. Cell Death Dis. 3:e2752012. View Article : Google Scholar : PubMed/NCBI

20 

Singh R and Cuervo AM: Lipophagy: Connecting autophagy and lipid metabolism. Int J Cell Biol. 2012:2820412012. View Article : Google Scholar : PubMed/NCBI

21 

Song S, Andrikopoulos S, Filippis C, Thorburn AW, Khan D and Proietto J: Mechanism of fat-induced hepatic gluconeogenesis: Effect of metformin. Am J Physiol Endocrinol Metab. 281:E275–E282. 2001.PubMed/NCBI

22 

Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS and Bae JW: An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 63:727–735. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Anthony J, Kelkar A, Wilankar C, Ranjith V, Bhumra SK, Mutt SJ, Deka N, Sivaramakrishnan H, Sharma S and Marita AR: Discovery of p1736, a novel antidiabetic compound that improves peripheral insulin sensitivity in mice models. PLoS One. 8:e779462013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li M, Sharma A, Yin C, Tan X and Xiao Y: Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. Mol Med Rep 16: 680-686, 2017.
APA
Li, M., Sharma, A., Yin, C., Tan, X., & Xiao, Y. (2017). Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. Molecular Medicine Reports, 16, 680-686. https://doi.org/10.3892/mmr.2017.6637
MLA
Li, M., Sharma, A., Yin, C., Tan, X., Xiao, Y."Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice". Molecular Medicine Reports 16.1 (2017): 680-686.
Chicago
Li, M., Sharma, A., Yin, C., Tan, X., Xiao, Y."Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice". Molecular Medicine Reports 16, no. 1 (2017): 680-686. https://doi.org/10.3892/mmr.2017.6637
Copy and paste a formatted citation
x
Spandidos Publications style
Li M, Sharma A, Yin C, Tan X and Xiao Y: Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. Mol Med Rep 16: 680-686, 2017.
APA
Li, M., Sharma, A., Yin, C., Tan, X., & Xiao, Y. (2017). Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice. Molecular Medicine Reports, 16, 680-686. https://doi.org/10.3892/mmr.2017.6637
MLA
Li, M., Sharma, A., Yin, C., Tan, X., Xiao, Y."Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice". Molecular Medicine Reports 16.1 (2017): 680-686.
Chicago
Li, M., Sharma, A., Yin, C., Tan, X., Xiao, Y."Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD‑induced obese mice". Molecular Medicine Reports 16, no. 1 (2017): 680-686. https://doi.org/10.3892/mmr.2017.6637
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team