Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The adipocyte-secreted protein Acrp30 enhances hepatic insulin action

Nature Medicine volume 7, pages 947–953 (2001)Cite this article

Abstract

Acrp30 is a circulating protein synthesized in adipose tissue. A single injection in mice of purified recombinant Acrp30 leads to a 2–3-fold elevation in circulating Acrp30 levels, which triggers a transient decrease in basal glucose levels. Similar treatment in ob/ob, NOD (non-obese diabetic) or streptozotocin-treated mice transiently abolishes hyperglycemia. This effect on glucose is not associated with an increase in insulin levels. Moreover, in isolated hepatocytes, Acrp30 increases the ability of sub-physiological levels of insulin to suppress glucose production. We thus propose that Acrp30 is a potent insulin enhancer linking adipose tissue and whole-body glucose metabolism.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Purification of Acrp30 from serum-free HEK 293-T culture supernatant.
Figure 2: Effect of Acrp30 injection on serum glucose levels in mice.
Figure 3: Control injections demonstrating the specificity of the full-length Acrp30 injections.
Figure 4: Effects of Acrp30 injection on serum hormone, metabolite and glycogen levels in male C57Bl/6J mice.
Figure 5: Insulin-dose–dependent effects of Acrp30 on hepatic glucose production measured on isolated primary hepatocytes.
Figure 6: Effects of long-term caloric restriction and thiazolidinedione administration on circulating Acrp30 levels.

Similar content being viewed by others

References

  1. Mohamed-Ali, V., Pinkney, J.H. & Coppack, S.W. Adipose tissue as an endocrine and paracrine organ. Int. J. Obes. Relat. Metab. Disord. 22, 1145–1158 (1998).

    Article  CAS  Google Scholar 

  2. Havel, P.J. Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc. Nutr. Soc. 59, 359–371 (2000).

    Article  CAS  Google Scholar 

  3. Ahima, R.S. & Flier, J.S. Adipose Tissue as an Endocrine Organ. Trends Endocrinol. Metab. 11, 327–332 (2000).

    Article  CAS  Google Scholar 

  4. Kahn, B.B. & Flier, J.S. Obesity and insulin resistance. J. Clin. Invest. 106, 473–481 (2000).

    Article  CAS  Google Scholar 

  5. Ganda, O.P. Lipoatrophy, lipodystrophy, and insulin resistance. Ann. Intern. Med. 133, 304–306 (2000).

    Article  CAS  Google Scholar 

  6. Shimomura, I., Hammer, R.E., Ikemoto, S., Brown, M.S. & Goldstein, J.L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401, 73–76 (1999).

    Article  CAS  Google Scholar 

  7. Gavrilova, O. et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J. Clin. Invest. 105, 271–278 (2000).

    Article  CAS  Google Scholar 

  8. Scherer, P.E., Williams, S., Fogliano, M., Baldini, G. & Lodish, H.F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 270, 26746–26749 (1995).

    Article  CAS  Google Scholar 

  9. Hu, E., Liang, P. & Spiegelman, B.M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271, 10697–10703 (1996).

    Article  CAS  Google Scholar 

  10. Maeda, K. et al. 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 (1997).

    Article  Google Scholar 

  11. Nakano, Y., Tobe, T., Choi-Miura, N.H., Mazda, T. & Tomita, M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. (Tokyo) 120, 803–812 (1996).

    Article  CAS  Google Scholar 

  12. Reichenberger, E. et al. Genomic organization and full-length cDNA sequence of human collagen X. FEBS Lett. 311, 305–310 (1992).

    Article  CAS  Google Scholar 

  13. Reid, K.B., Gagnon, J. & Frampton, J. Completion of the amino acid sequences of the A and B chains of subcomponent C1q of the first component of human complement. Biochem. J. 203, 559–569 (1982).

    Article  CAS  Google Scholar 

  14. Kondo, N. & Kondo, J. Identification of novel blood proteins specific for mammalian hibernation. J. Biol. Chem. 267, 473–478 (1992).

    CAS  PubMed  Google Scholar 

  15. Shapiro, L. & Scherer, P.E. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. 8, 335–338 (1998).

    Article  CAS  Google Scholar 

  16. Hotta, K. et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler. Thromb. Vasc. Biol. 20, 1595–1599 (2000).

    Article  CAS  Google Scholar 

  17. Fruebis, J. et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc. Natl. Acad. Sci. USA 98, 2005–2010 (2001).

    Article  CAS  Google Scholar 

  18. Meng, Y.G., Liang, J., Wong, W.L. & Chisholm, V. Green fluorescent protein as a second selectable marker for selection of high producing clones from transfected CHO cells. Gene 242, 201–207 (2000).

    Article  CAS  Google Scholar 

  19. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1988).

    Google Scholar 

  20. Cherrington, A.D. Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo. Diabetes 48, 1198–1214 (1999).

    Article  CAS  Google Scholar 

  21. Seoane, J. et al. Metabolic impact of adenovirus-mediated overexpression of the glucose-6- phosphatase catalytic subunit in hepatocytes. J. Biol. Chem. 272, 26972–26977 (1997).

    Article  CAS  Google Scholar 

  22. Masoro, E.J. Caloric restriction and aging: an update. Exp. Gerontol. 35, 299–305 (2000).

    Article  CAS  Google Scholar 

  23. Gupta, G. et al. Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation. Am. J. Physiol. Endocrinol. Metab. 278, E985–991. (2000).

    Article  CAS  Google Scholar 

  24. Day, C. Thiazolidinediones: A new class of antidiabetic drugs. Diabet. Med. 16, 179–192 (1999).

    Article  CAS  Google Scholar 

  25. Reginato, M.J. & Lazar, M.A. Mechanisms by which thiazolidinediones enhance insulin action. Trends Endocrinol. Metab. 10, 9–13 (1999).

    Article  CAS  Google Scholar 

  26. Chao, L. et al. Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J. Clin. Invest. 106, 1221–1228 (2000).

    Article  CAS  Google Scholar 

  27. Kissebah, A.H. et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc. Natl. Acad. Sci. USA 97, 14478–14483 (2000).

    Article  CAS  Google Scholar 

  28. Das, K., Lin, Y., Widen, E., Zhang, Y. & Scherer, P.E. Chromosomal localization, expression pattern and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30. Biochem. Biophys. Res. Comm. 280, 1120–1129 (2001).

    Article  CAS  Google Scholar 

  29. Takahashi, M. et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int. J. Obes. Relat. Metab. Disord. 24, 861–868 (2000).

    Article  CAS  Google Scholar 

  30. Lang, C.H., Bagby, G.J., Buday, A.Z. & Spitzer, J.J. The contribution of gluconeogenesis to glycogen repletion during glucose infusion in endotoxemia. Metabolism 36, 180–187 (1987).

    Article  CAS  Google Scholar 

  31. Bligh, E. & Dyer, W.J. Rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911–917 (1959).

    Article  CAS  Google Scholar 

  32. Berry, M.N. & Friend, B.S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structure study. J. Cell. Biol. 43, 506–520 (1969).

    Article  CAS  Google Scholar 

  33. Leffert, H.L., Koch, K.S., Moran, T. & Williams, M. Liver cells. Methods Enzymol. 58, 536–544 (1979).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank L. Rossetti, M. Charron and D. Stein for helpful discussions; D. Harrison and S. Klebanov for control and food-restricted serum samples; S. Nathenson and T. DiLorenzo for providing NOD mice for experiments; D. Neufeld for his help in isolating rat primary hepatocytes; and F. Mancia and A. Nemes for vector pFM1. This work was supported by the Training Program in Cellular & Molecular Biology & Genetics (T32-GM07491 to A.H.B.), the Hormones/Membrane Interactions Training Grant (NIH-T32 DK 07513-15 to T.C.), grants from the American Diabetes Association (to P.E.S.) and a NIH grant from the NIDDK (1R01-DK55758 to P.E.S.).

Author information

Author notes

  1. Anders H. Berg and Terry P. Combs: A.H.B. and T.P.C. contributed equally to this study.

Authors and Affiliations

  1. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA

    Anders H. Berg, Terry P. Combs & Philipp E. Scherer

  2. Department of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, New York, USA

    Xueliang Du & Michael Brownlee

  3. Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, USA

    Michael Brownlee & Philipp E. Scherer

Authors
  1. Anders H. Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Terry P. Combs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xueliang Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Brownlee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Philipp E. Scherer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philipp E. Scherer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berg, A., Combs, T., Du, X. et al. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7, 947–953 (2001). https://doi.org/10.1038/90992

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/90992

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing