Skip to main content
SpringerLink
Log in

Mitochondrial development and the influence of its dysfunction during rat adipocyte differentiation

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Mitochondrial biogenesis is inherent to adipocyte differentiation. Mitochondrial dysfunction leads to abnormal lipid accumulation or the deterioration of the differentiation process. The aim of this study is to investigate the mitochondrial development during the differentiation of rat primary adipocytes and the effect of mitochondrial dysfunction on this process. We found, for the first time, that the number of mitochondria markedly increased during adipocyte differentiation by transmission electron microscopy. By immunofluorescence staining that the protein content of Cyt c increased in differentiated adipocyte in comparison with preadipocyte. The mRNA expression levels of mitochondrial gene including cytochromes c (Cyt c), malate dehydrogenases (MDH), and peroxisome proliferator activated receptor (PPAR) γ coactivator-1β (PGC-1β) significantly increased along with the proceeding of adipocyte differentiation. The damage to mitochondrial respiratory chain function by rotenone caused significant decrease in gene expressions including mitochondrial MDH and PGC-1β, and PPARγ, CAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein-1c (SREBP-1c), which are known as transcription factors of differentiation, and differentiation marker gene named fatty acid synthetase. Moreover, an apparent decrease was found in the synthesis of triglyceride and ATP due to the damage to mitochondria by rotenone. Based on the above results, our present study revealed that the density and oxidative capacity of mitochondrial markedly increased during primary adipocyte differentiation, and on the other hand, we suggested that mitochondria dysfunction might inhibit the differentiation process.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

Cyt c :

Cytochromes c

C/EBPα:

CAAT/enhancer binding protein α

PPARγ:

Peroxisome proliferator activated receptor γ

SREBP-1c:

Sterol regulatory element binding protein-1c

FAS:

Fatty acid synthetase

LPL:

Lipoprotein lipase

PGC-1:

Peroxisome proliferator-activated receptor γ coactivator-1

PRC:

PGC-1-related coactivator

MDH:

Malate dehydrogenases

MRC:

Mitochondrial respiratory chain

CREB:

cAMP-response element binding protein

References

  1. Desvergne B, Michalik L, Wahli W (2006) Transcriptional regulation of metabolism. J Physiol Rev 86:465–514

    Article  CAS  Google Scholar 

  2. Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809

    CAS  PubMed  Google Scholar 

  3. Rosen ED, Hsu CH, Wang XZ, Sakai SC, Freeman MW, Gonzalez FJ, Spiegelman BM (2002) C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway. Genes Dev 16:22–26

    Article  CAS  PubMed  Google Scholar 

  4. Madsen L, Petersen RK, Sorensen MB, Jorgensen C, Hanllenborg P, Pridal L, Fleckner J, Amri EZ, Krieg P, Furstenberger G, Berge RK, Kristiansen K (2003) Adipocyte differentiation of 3T3–L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process. J Biochem 375:539–549

    Article  CAS  Google Scholar 

  5. Tong Q, Tsai J, Tan G, Dalgin G, Hotamisligil GS (2005) Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation. Mol Cell Biol 25:706–715

    Article  CAS  PubMed  Google Scholar 

  6. Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Sarah N, Czech M, Corvera S (2003) Mitochondrial Biogenesis and remolding during Adipogenesis and in Response to the Insulin Sensitiser Rosiglitazone. Mol Cel Biol J 23:1085–1094

    Article  CAS  Google Scholar 

  7. McKay RM, McKay JP, Avery R, Graff JM (2003) C. elegans: a model for exploring the genetics of fat storage. J Dev Cell 4:131–142

    Article  CAS  Google Scholar 

  8. Shi XR, Burkart A, Nicoloro SM, Czech MP, Straubhaar J, Corvera S (2008) Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells. J Biol Chem 283:30658–30667

    Article  CAS  PubMed  Google Scholar 

  9. Vankoningsloo S, Pauw AD, Houbion A, Tejerina S, Demazy C, Longueville FD, Bertholet V, Renard P, Remacle J, Holvoet P, Raes M, Arnould T (2006) CREB activation induced by mitochondrial dysfunction triggers triglyceride accumulation in 3T3–L1 preadipocytes. J Cell Sci 119:1266–1282

    Article  CAS  PubMed  Google Scholar 

  10. Kim T, Leitner W, Adochio R, Draznin B (2009) Knockdown of JNK rescues 3T3–L1 adipocytes from insulin resistance induced by mitochondrial dysfunction. Biochem Biophys Res Commun 378:772–776

    Article  CAS  PubMed  Google Scholar 

  11. Sébastien V, Marie SP, Christophe L, Gilson A, Pauw AD, Renard P, Demazy C, Houbion A, Raes M, Arnould T (2005) Mitochondrial dysfunction induces triglyceride accumulation in 3T3–L1 cells: role of fatty acid β-oxidation and glucose. J Lipid Res 46:1133–1149

    Article  Google Scholar 

  12. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1a and SIRT1. Nature 434:113–118

    Article  CAS  PubMed  Google Scholar 

  13. Lin JD, Wu H, Tarr PT (2002) Transcriptional co-activator PGC-1a drives the formation of slow-twitch muscle fibers. Nature 418:797–801

    Article  CAS  PubMed  Google Scholar 

  14. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang RJ, Newgard CB, Spiegelman BM (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor coactivators1a and 1b (PGC-1a and PGC-1b) in muscle cells. J Biol Chem 278:26597–26603

    Article  CAS  PubMed  Google Scholar 

  15. Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM (2006) Complementary action of the PGC-1 coactivator in mitochondrial biogenesis and brown fat differentiation. J Cell Metabolism 4:333–341

    Article  Google Scholar 

  16. Kamei Y, Ohizumi H, Fujitani Y, Tomoyuki N, Toshiya T, Takahashi N, Kawada T, Miyoshi M, Ezaki O, Kakizuka A (2003) PPARγ coactivator 1β/ERR ligand1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. PNAS 100:12378–12383

    Article  CAS  PubMed  Google Scholar 

  17. Stocchi V, Cucchiarini L, Magnani M, Chiarantini L, Palma P, Crescentini G (1985) Simultaneous extraction and reverse-phase high performance liquid chromatographic determination of adenine and pyridine nucleotides in human red blood cells. Anal Biochem 146:118–124

    Article  CAS  PubMed  Google Scholar 

  18. Ramirez-Zacarias JL, Castro-Munozledo F, Kuri-Harcuch W (1992) Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O. Histochemistry 97:493–497

    Article  CAS  PubMed  Google Scholar 

  19. Peterson GL (1977) A simplification of the protein assay of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356

    Article  CAS  PubMed  Google Scholar 

  20. Kudo M, Sugawara A, Uruno A, Takeuchi K, Ito S (2004) Transcription suppression of peroxisome proliferator-activated receptor 2 gene expression by tumor necrosis factor via an inhibition of CCAAT/enhancer-binding protein during the early stage of adipocyte differentiation. Endocrinology 145:4948–4956

    Article  CAS  PubMed  Google Scholar 

  21. Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277:30409–30412

    Article  CAS  PubMed  Google Scholar 

  22. Luo GF, Yu TY, Wen XH, Yang GS (2008) Alteration of mitochondrial oxidative capacity during porcine preadipocyte differentiation and in response to leptin. Mol Cell Biochem 307:83–91

    Article  CAS  PubMed  Google Scholar 

  23. Omatsu-Kanbe M, Inoue K, Yamamoto T et al (2006) Effect of ATP on preadipocyte migration and adipocyte differentiation by activating P2Y receptors in 3T3–L1 cells. Biochem J 393:171–180

    Article  CAS  PubMed  Google Scholar 

  24. Vianna CR, Huntgeburth M, Coppari R, Choi C, Lin J, Krauss S, Barbatelli G, Tzameli I, Kim Y, Cinti S (2006) Hypomorphic mutation of PGC-1β causes mitochondrial dysfunction and liver insulin resistance. Cell Metab 4:453–464

    Article  CAS  PubMed  Google Scholar 

  25. Savagner F, Mirebeau D, Jacques C, Guyetant S, Catherine Morgan, Franc B, Reynier P, Malthiery Y (2003) PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma. Biochem Biophys Res Commun 310:779–784

    Article  CAS  PubMed  Google Scholar 

  26. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr Guoliang Meng and Dr Xuebo Liu for their kind help in reviewing the manuscript. This study was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2006AA10Z138) and China Postdoctoral Science Foundation funded project (No. 20080431254).

Author information

Authors and Affiliations

  1. Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, 712100, Yangling, Shaanxi, China

    Rong-hua Lu, Hong Ji, Zhi-guang Chang, Shang-shun Su & Gong-she Yang

Authors
  1. Rong-hua Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-guang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shang-shun Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gong-she Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gong-she Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, Rh., Ji, H., Chang, Zg. et al. Mitochondrial development and the influence of its dysfunction during rat adipocyte differentiation. Mol Biol Rep 37, 2173–2182 (2010). https://doi.org/10.1007/s11033-009-9695-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9695-z

Keywords

Search

Navigation