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Genes & Nutrition

, Volume 2, Issue 1, pp 41–45 | Cite as

Adipose tissue expandability and the metabolic syndrome

  • Marc Slawik
  • Antonio J. Vidal-Puig
Proceedings

Introduction

The safest place to store lipids is the white adipose tissue, but its storage capacity may become saturated resulting in excess of fat “overspilled” to non-adipose tissues. This overspill of fat occurs in apparently opposite pathological states such as lipodistrophy or obesity. When the excess of energy is redirected towards peripheral organs, their initial response is to facilitate the storage of the surplus in the form of triacylglycerol, but the limited triacylglycerol buffer capacity becomes saturated soon. Under these conditions excess of lipids enter alternative non-oxidative pathways that result in production of toxic reactive lipid species that induce organ specific toxic responses leading to apoptosis. Reactive lipids can accumulate in non-adipose tissues of metabolically relevant organs such as pancreatic beta cells, liver, heart and skeletal muscle leading to lipotoxicity, a process that contributes substantially to the pathophysiology of insulin resistance,...

Keywords

Adipose Tissue Beta Cell White Adipose Tissue Lipodystrophy Adipose Tissue Expandability 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Marc Slawik was supported by a fellowship from the Fritz Thyssen Foundation, Germany.

References

  1. 1.
    Abu-Elheiga L, Matzuk MM, Abo-Hashema KA, Wakil SJ (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291:2613–2616PubMedCrossRefGoogle Scholar
  2. 2.
    Barak Y, Nelson MC, Ong ES, Jones YZ, Ruiz-Lozano P, Chien KR, Koder A, Evans RM (1999) PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4:585–595PubMedCrossRefGoogle Scholar
  3. 3.
    Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims EA, Poehlman ET (2001) What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab 86:1020–1025PubMedCrossRefGoogle Scholar
  4. 4.
    Cock TA, Houten SM, Auwerx J (2004) Peroxisome proliferator-activated receptor-gamma: too much of a good thing causes harm. EMBO Rep 5:142–147PubMedCrossRefGoogle Scholar
  5. 5.
    Escher P, Braissant O, Basu-Modak S, Michalik L, Wahli W, Desvergne B (2001) Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding. Endocrinology 142:4195–4202PubMedCrossRefGoogle Scholar
  6. 6.
    Garg A (2000) Lipodystrophies. Am J Med 108:143–152PubMedCrossRefGoogle Scholar
  7. 7.
    Gray SL, Dalla Nora E, Vidal-Puig AJ (2005) Mouse models of PPAR-gamma deficiency: dissecting PPAR-gamma’s role in metabolic homoeostasis. Biochem Soc Trans 33:1053–1058PubMedCrossRefGoogle Scholar
  8. 8.
    Holm C, Osterlund T, Laurell H, Contreras JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr 20:365–393PubMedCrossRefGoogle Scholar
  9. 9.
    Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM (1998) Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 101:1–9PubMedGoogle Scholar
  10. 10.
    Koutnikova H, Cock TA, Watanabe M, Houten SM, Champy MF, Dierich A, Auwerx J (2003) Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice. Proc Natl Acad Sci USA 100:14457–14462PubMedCrossRefGoogle Scholar
  11. 11.
    Kressler D, Schreiber SN, Knutti D, Kralli A (2002) The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha. J Biol Chem 277:13918–13925PubMedCrossRefGoogle Scholar
  12. 12.
    Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, Satoh S, Nakano R, Ishii C, Sugiyama T, Eto K, Tsubamoto Y, Okuno A, Murakami K, Sekihara H, Hasegawa G, Naito M, Toyoshima Y, Tanaka S, Shiota K, Kitamura T, Fujita T, Ezaki O, Aizawa S, Kadowaki T et al. (1999) PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 4:597–609PubMedCrossRefGoogle Scholar
  13. 13.
    Le Lay S, Lefrere I, Trautwein C, Dugail I, Krief S (2002) Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. J Biol Chem 277:35625–35634PubMedCrossRefGoogle Scholar
  14. 14.
    Lin J, Puigserver P, Donovan J, Tarr P, Spiegelman BM (2002a) Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 277:1645–1648PubMedCrossRefGoogle Scholar
  15. 15.
    Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002b) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801PubMedCrossRefGoogle Scholar
  16. 16.
    Medina-Gomez G, Virtue S, Lelliott C, Boiani R, Campbell M, Christodoulides C, Perrin C, Jimenez-Linan M, Blount M, Dixon J, Zahn D, Thresher RR, Aparicio S, Carlton M, Colledge WH, Kettunen MI, Seppanen-Laakso T, Sethi JK, O’Rahilly S, Brindle K, Cinti S, Oresic M, Burcelin R, Vidal-Puig A (2005) The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform. Diabetes 54:1706–1716PubMedCrossRefGoogle Scholar
  17. 17.
    Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O’Rahilly S, Montague C, Vidal-Puig AJ (2003) Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem J 373:155–165PubMedCrossRefGoogle Scholar
  18. 18.
    Michael LF, Wu Z, Cheatham RB, Puigserver P, Adelmant G, Lehman JJ, Kelly DP, Spiegelman BM (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98:3820–3825PubMedCrossRefGoogle Scholar
  19. 19.
    Molina JM, Ciaraldi TP, Brady D, Olefsky JM (1989) Decreased activation rate of insulin-stimulated glucose transport in adipocytes from obese subjects. Diabetes 38:991–995PubMedCrossRefGoogle Scholar
  20. 20.
    Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101:1354–1361PubMedGoogle Scholar
  21. 21.
    Olefsky JM (1977) Insensitivity of large rat adipocytes to the antilipolytic effects of insulin. J Lipid Res 18:459–464PubMedGoogle Scholar
  22. 22.
    Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Hayflick L, Butler RN, Allison DB, Ludwig DS (2005) A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352:1138–1145PubMedCrossRefGoogle Scholar
  23. 23.
    Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4:611–617PubMedCrossRefGoogle Scholar
  24. 24.
    Savage DB, Murgatroyd PR, Chatterjee VK, O’Rahilly S (2005) Energy expenditure and adaptive responses to an acute hypercaloric fat load in humans with lipodystrophy. J Clin Endocrinol Metab 90:1446–1452PubMedCrossRefGoogle Scholar
  25. 25.
    Sewter C, Berger D, Considine RV, Medina G, Rochford J, Ciaraldi T, Henry R, Dohm L, Flier JS, O’Rahilly S, Vidal-Puig AJ (2002) Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha. Diabetes 51:1035–1041PubMedCrossRefGoogle Scholar
  26. 26.
    Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV Jr (2000) Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 25:87–90PubMedCrossRefGoogle Scholar
  27. 27.
    Spiegelman BM (1998) PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 47:507–514PubMedCrossRefGoogle Scholar
  28. 28.
    Tabarin A, Diz-Chaves Y, Carmona Mdel C, Catargi B, Zorrilla EP, Roberts AJ, Coscina DV, Rousset S, Redonnet A, Parker GC, Inoue K, Ricquier D, Penicaud L, Kieffer BL, Koob GF (2005) Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a “thrifty gene”. Diabetes 54:3510–3516PubMedCrossRefGoogle Scholar
  29. 29.
    Vidal-Puig A, Jimenez-Linan M, Lowell BB, Hamann A, Hu E, Spiegelman B, Flier JS, Moller DE (1996) Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Invest 97:2553–2561PubMedCrossRefGoogle Scholar
  30. 30.
    Wang S, Subramaniam A, Cawthorne MA, Clapham JC (2003) Increased fatty acid oxidation in transgenic mice overexpressing UCP3 in skeletal muscle. Diabetes Obes Metab 5:295–301PubMedCrossRefGoogle Scholar
  31. 31.
    Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43:1498–1506PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Clinical BiochemistryUniversity of CambridgeCambridgeUK
  2. 2.Clinical BiochemistryAddenbrooke’s Hospital CambridgeCambridgeUK

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