Skip to main content

Advertisement

SpringerLink
Log in

Uncovering the Role of Glycogen in Brown Adipose Tissue

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

The presence of glycogen in the brown adipose tissue (BAT) has been described 60 years ago. However, the role of this energetic storage in brown adipocytes has been long time underestimated. We have recently shown that during brown adipocyte differentiation in the embryo, glycogen accumulates and is degraded by glycophagy, a dynamic essential for lipid droplets biogenesis. Recent studies have shown that the storage and degradation of triglycerides in BAT are not essential for the activation of BAT in response to cold exposure in adults, and that glycogen can compensate for their absence. In this review, we report the recent advances related to the importance of glycogen in brown adipocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009 Apr 9;360(15):1509–17.

    Article  CAS  Google Scholar 

  2. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JMAFL, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009 Apr 9;360(15):1500–8.

    Article  Google Scholar 

  3. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009 Apr 9;360(15):1518–25.

    Article  CAS  Google Scholar 

  4. Sanchez-Gurmaches J, Hung C-M, Guertin DA. Emerging Complexities in Adipocyte Origins and Identity. Trends Cell Biol. 2016;26(5):313–26.

    Article  CAS  Google Scholar 

  5. Nishimoto Y, Tamori Y. CIDE Family-Mediated Unique Lipid Droplet Morphology in White Adipose Tissue and Brown Adipose Tissue Determines the Adipocyte Energy Metabolism. J Atheroscler Thromb. 2017 Oct 1;24(10):989–98.

    Article  CAS  Google Scholar 

  6. Alexander G. Energy metabolism in the starved new-born lamb. Aust J Agric Res. 1962;13:144–64.

    Article  CAS  Google Scholar 

  7. Dawkins MJ, Scopes JW. Non-shivering thermogenesis and brown adipose tissue in the human new-born infant. Nature. 1965 Apr 10;206(980):201–2.

    Article  CAS  Google Scholar 

  8. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011 Feb;17(2):200–5.

    Article  CAS  Google Scholar 

  9. Blondin DP, Frisch F, Phoenix S, Guérin B, Turcotte ÉE, Haman F, et al. Inhibition of intracellular triglyceride lipolysis suppresses cold-induced brown adipose tissue metabolism and increases shivering in humans. Cell Metab. 2017 07;25(2):438–47.

  10. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006 May 5;312(5774):734–7.

    Article  CAS  Google Scholar 

  11. Osuga J, Ishibashi S, Oka T, Yagyu H, Tozawa R, Fujimoto A, et al. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):787–92.

    Article  CAS  Google Scholar 

  12. Schreiber R, Diwoky C, Schoiswohl G, Feiler U, Wongsiriroj N, Abdellatif M, et al. Cold-induced thermogenesis depends on atgl-mediated lipolysis in cardiac muscle, but not brown adipose tissue. Cell Metab. 2017 Nov 7;26(5):753–763.e7.

  13. Wang SP, Laurin N, Himms-Hagen J, Rudnicki MA, Levy E, Robert MF, et al. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res. 2001 Feb;9(2):119–28.

    Article  CAS  Google Scholar 

  14. Ahmadian M, Abbott MJ, Tang T, Hudak CSS, Kim Y, Bruss M, et al. Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype. Cell Metab. 2011 Jun 8;13(6):739–48.

    Article  CAS  Google Scholar 

  15. Shin H, Ma Y, Chanturiya T, Cao Q, Wang Y, Kadegowda AKG, et al. Lipolysis in brown adipocytes is not essential for cold-induced thermogenesis in mice. Cell Metab. 2017 Nov 7;26(5):764–777.e5.

  16. Heine M, Fischer AW, Schlein C, Jung C, Straub LG, Gottschling K, et al. Lipolysis triggers a systemic insulin response essential for efficient energy replenishment of activated brown adipose tissue in mice. Cell Metab. 2018 02;28(4):644–655.e4.

  17. Simcox J, Geoghegan G, Maschek JA, Bensard CL, Pasquali M, Miao R, et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab. 2017 Sep 5;26(3):509–522.e6.

  18. Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, et al. Human brown adipocyte thermogenesis is driven by β2-AR stimulation. Cell Metab. 2020 Aug 4;32(2):287–300.e7.

  19. Weinstock PH, Levak-Frank S, Hudgins LC, Radner H, Friedman JM, Zechner R, et al. Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10261–6.

    Article  CAS  Google Scholar 

  20. Chondronikola M, Volpi E, Børsheim E, Porter C, Saraf MK, Annamalai P, et al. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans. Cell Metab. 2016 Jun 14;23(6):1200–6.

    Article  CAS  Google Scholar 

  21. Bartelt A, Weigelt C, Cherradi ML, Niemeier A, Tödter K, Heeren J, et al. Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning. Biochim Biophys Acta. 2013 May;1831(5):934–42.

    Article  CAS  Google Scholar 

  22. Martinez-Lopez N, Garcia-Macia M, Sahu S, Athonvarangkul D, Liebling E, Merlo P, et al. Autophagy in the CNS and Periphery Coordinate Lipophagy and Lipolysis in the Brown Adipose Tissue and Liver. Cell Metab. 2016 Jan 12;23(1):113–27.

    Article  CAS  Google Scholar 

  23. Chitraju C, Fischer AW, Farese RV, Walther TC. Lipid droplets in brown adipose tissue are dispensable for cold-induced thermogenesis. Cell Rep. 2020 nov 3; 33(5):108348.

  24. Bhatt-Wessel B, Jordan TW, Miller JH, Peng L. Role of DGAT enzymes in triacylglycerol metabolism. Arch Biochem Biophys. 2018 01;655:1–11.

  25. Mayeuf-Louchart A, Lancel S, Sebti Y, Pourcet B, Loyens A, Delhaye S, et al. Glycogen dynamics drives lipid droplet biogenesis during brown adipocyte differentiation. Cell Rep. 2019 Nov 5;29(6):1410–1418.e6.

  26. Napolitano L, Fawcett D. The fine structure of brown adipose tissue in the newborn mouse and rat. J Biophys Biochem Cytol. 1958 Nov 25;4(6):685–92.

    Article  CAS  Google Scholar 

  27. Revel JP, Napolitano L, Fawcett DW. Identification of glycogen in electron micrographs of thin tissue sections. J Biophys Biochem Cytol. 1960 Dec;8:575–89.

    Article  CAS  Google Scholar 

  28. Hankir MK, Klingenspor M. Brown adipocyte glucose metabolism: a heated subject. EMBO Rep. 2018;19(9).

  29. McNeill BT, Morton NM, Stimson RH. Substrate utilization by brown adipose tissue: what’s hot and what’s not? Front Endocrinol. 2020;11:571659.

    Article  Google Scholar 

  30. Creasey NH, Gray CH. Enzymes concerned in the synthesis of glycogen from glucose in the brown adipose tissue. Biochem J. 1951 Nov;50(1):74–81.

    Article  CAS  Google Scholar 

  31. Farkas V, Kelenyi G, Sandor A. A dramatic accumulation of glycogen in the brown adipose tissue of rats following recovery from cold exposure. Arch Biochem Biophys. 1999 May 1;365(1):54–61.

    Article  CAS  Google Scholar 

  32. Jakus PB, Sandor A, Janaky T, Farkas V. Cooperation between BAT and WAT of rats in thermogenesis in response to cold, and the mechanism of glycogen accumulation in BAT during reacclimation. J Lipid Res. 2008 Feb;49(2):332–9.

    Article  CAS  Google Scholar 

  33. Tuerkischer E, Wertheimer E. Glycogen and adipose tissue. J Physiol. 1942 Mar 31;100(4):385–409.

    Article  CAS  Google Scholar 

  34. Carmean CM, Bobe AM, Yu JC, Volden PA, Brady MJ. Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is mediated by insulin and catecholamines. PLoS One. 2013;8(7):e67807.

    Article  CAS  Google Scholar 

  35. Carmean CM, Huang YH, Brady MJ. Glycogen Repletion in Brown Adipose Tissue upon Refeeding Is Primarily Driven by Phosphorylation-Independent Mechanisms. PLoS One. 2016;11(5):e0156148.

    Article  Google Scholar 

  36. Hao Q, Yadav R, Basse AL, Petersen S, Sonne SB, Rasmussen S, et al. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2015 Mar 1;308(5):E380–92.

    Article  CAS  Google Scholar 

  37. Jiang S, Wells CD, Roach PJ. Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1. Biochem Biophys Res Commun. 2011 Sep 30;413(3):420–5.

    Article  CAS  Google Scholar 

  38. Liu J, Zhang C, Zhang B, Sheng Y, Xu W, Luo Y, et al. Comprehensive analysis of the characteristics and differences in adult and newborn brown adipose tissue (BAT): newborn BAT is a more active/dynamic BAT. Cells. 2020;14:9(1).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Univ. Lille, U1011 - EGID, F-59000, Lille, France

    Alicia Mayeuf-Louchart

  2. Inserm, U1011, F-59000, Lille, France

    Alicia Mayeuf-Louchart

  3. CHU Lille, Nom du Service hospitalier, F-59000, Lille, France

    Alicia Mayeuf-Louchart

  4. Institut Pasteur de Lille, F-59000, Lille, France

    Alicia Mayeuf-Louchart

Authors
  1. Alicia Mayeuf-Louchart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alicia Mayeuf-Louchart.

Additional information

Guest Editors: Meng Deng and Shihuan Kuang

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mayeuf-Louchart, A. Uncovering the Role of Glycogen in Brown Adipose Tissue. Pharm Res 38, 9–14 (2021). https://doi.org/10.1007/s11095-020-02979-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-020-02979-6

Key words

Search

Navigation