Serum Preadipocyte Factor-1 Concentrations in Females with Obesity and Type 2 Diabetes Mellitus: The Influence of Very Low Calorie Diet, Acute Hyperinsulinemia, and Fenofibrate Treatment

 

 Buy Article Permissions and Reprints

Abstract

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months’ treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients.

• References

• 1 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607
  CrossrefPubMedGoogle Scholar
• 2 Mraz M, Lacinova Z, Drapalova J, Haluzikova D, Horinek A, Matoulek M, Trachta P, Kavalkova P, Svacina S, Haluzik M. The effect of very-low-calorie diet on mRNA expression of inflammation-related genes in subcutaneous adipose tissue and peripheral monocytes of obese patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2011; 96: E606-E613
  CrossrefPubMedGoogle Scholar
• 3 O’Connell J, Lynch L, Hogan A, Cawood TJ, O’Shea D. Preadipocyte factor-1 is associated with metabolic profile in severe obesity. J Clin Endocrinol Metab 2011; 96: E680-E684
  CrossrefPubMedGoogle Scholar
• 4 Harp JB. New insights into inhibitors of adipogenesis. Curr Opin Lipidol 2004; 15: 303-307
  CrossrefPubMedGoogle Scholar
• 5 Wu Y, Zhou S, Smas CM. Downregulated expression of the secreted glycoprotein follistatin-like 1 (Fstl1) is a robust hallmark of preadipocyte to adipocyte conversion. Mech Dev 2010; 127: 183-202
  CrossrefPubMedGoogle Scholar
• 6 Jing K, Heo JY, Song KS, Seo KS, Park JH, Kim JS, Jung YJ, Jo DY, Kweon GR, Yoon WH, Hwang BD, Lim K, Park JI. Expression regulation and function of Pref-1 during adipogenesis of human mesenchymal stem cells (MSCs). Biochim Biophys Acta 2009; 1791: 816-826
  CrossrefPubMedGoogle Scholar
• 7 De Zegher F, Díaz M, Sebastiani G, Martín-Ancel A, Sánchez-Infantes D, López-Bermejo A, Ibáñez L. Abundance of circulating preadipocyte factor 1 in early life. Diabetes Care 2012; 35: 848-849
  CrossrefPubMedGoogle Scholar
• 8 Villena JA, Kim KH, Sul HS. Pref-1 and ADSF/resistin: two secreted factors inhibiting adipose tissue development. Horm Metab Res 2002; 34: 664-670
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Mei B, Zhao L, Chen L, Sul HS. Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing. Biochem J 2002; 364: 137-144
  CrossrefPubMedGoogle Scholar
• 10 Kim KA, Kim JH, Wang Y, Sul HS. Pref-1 (preadipocyte factor 1) activates the MEK/extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation. Mol Cell Biol 2007; 27: 2294-2308
  CrossrefPubMedGoogle Scholar
• 11 Sul HS. Minireview. Pref-1: role in adipogenesis and mesenchymal cell fate. Mol Endocrinol 2009; 23: 1717-1725
  CrossrefPubMedGoogle Scholar
• 12 Gustafson B, Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J Biol Chem 2006; 281: 9507-9516
  CrossrefPubMedGoogle Scholar
• 13 Tseng YH, Butte AJ, Kokkotou E, Yechoor VK, Taniguchi CM, Kriauciunas KM, Cypess AM, Niinobe M, Yoshikawa K, Patti ME, Kahn CR. Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin. Nat Cell Biol 2005; 7: 601-611
  CrossrefPubMedGoogle Scholar
• 14 Gong H, Ni Y, Guo X, Fei L, Pan X, Guo M, Chen R. Resistin promotes 3T3-L1 preadipocyte differentiation. Eur J Endocrinol 2004; 150: 885-892
  CrossrefPubMedGoogle Scholar
• 15 Gustafson B, Smith U. Activation of canonical wingless-type MMTV integration site family (Wnt) signaling in mature adipocytes increases beta-catenin levels and leads to cell dedifferentiation and insulin resistance. J Biol Chem 2010; 285: 14031-14041
  CrossrefPubMedGoogle Scholar
• 16 Diaz Sanchez-Bustamante C, Kelm JM, Egermann M, Djonov V, Fussenegger M. Ectopic expression of delta FBJ murine osteosarcoma viral oncogene homolog B mediates transdifferentiation of adipose-like spheroids into osteo-like microtissues. Tissue Eng Part A 2008; 14: 1377-1394
  CrossrefPubMedGoogle Scholar
• 17 Nielsen JH, Svensson C, Galsgaard ED, Møldrup A, Billestrup N. Beta cell proliferation and growth factors. J Mol Med (Berl) 1999; 77: 62-66
  CrossrefPubMedGoogle Scholar
• 18 Moon YS, Smas CM, Lee K, Villena JA, Kim KH, Yun EJ, Sul HS. Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity. Mol Cell Biol 2002; 22: 5585-5592
  CrossrefPubMedGoogle Scholar
• 19 Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS. Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). J Clin Invest 2003; 111: 453-461
  CrossrefPubMedGoogle Scholar
• 20 Villena JA, Choi CS, Wang Y, Kim S, Hwang YJ, Kim YB, Cline G, Shulman GI, Sul HS. Resistance to high fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing Pref-1: a new model of partial lipodystrophy. Diabetes 2008; 57: 3258-3266
  CrossrefPubMedGoogle Scholar
• 21 Giralt M, Domingo P, Guallar JP, Rodriguez de la Concepcion ML, Alegre M, Domingo JC, Villarroya F. HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV-1/HAART-associated lipodystrophy. Antivir Ther 2006; 11: 729-740
  PubMedGoogle Scholar
• 22 Koutkia P, Grinspoon S. HIV-associated lipodystrophy: pathogenesis, prognosis, treatment, and controversies. Annu Rev Med 2004; 55: 303-317
  CrossrefPubMedGoogle Scholar
• 23 Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, Herbert JM, Winegar DA, Willson TM, Fruchart JC, Berge RK, Staels B. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem 2000; 275: 16638-16642
  CrossrefPubMedGoogle Scholar
• 24 Cabrero A, Alegret M, Sánchez RM, Adzet T, Laguna JC, Vázquez M. Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes. Diabetes 2001; 50: 1883-1890
  CrossrefPubMedGoogle Scholar
• 25 Haluzik MM, Anderlova K, Dolezalova R, Adamikova A, Haluziková D, Housova J, Svacina S, Haluzik M. Serum adipocyte fatty acid binding protein levels in patients with type 2 diabetes mellitus and obesity: the influence of fenofibrate treatment. Physiol Res 2009; 58: 93-99
  PubMedGoogle Scholar
• 26 Anderlova K, Dolezalova R, Housova J, Bosanska L, Haluzikova D, Kremen J, Skrha J, Haluzik M. Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissuederived hormones in obese women with type 2 diabetes. Physiol Res 2007; 56: 579-586
  PubMedGoogle Scholar
• 27 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  Google Scholar
• 28 Shimomura I, Hammer RE, Richardson JA, Ikemoto S, Bashmakov Y, Goldstein JL, Brown MS. Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev 1998; 12: 3182-3194
  CrossrefPubMedGoogle Scholar
• 29 Wang MY, Grayburn P, Chen S, Ravazzola M, Orci L, Unger RH. Adipogenic capacity and the susceptibility to type 2 diabetes and metabolic syndrome. Proc Natl Acad Sci USA 2008; 105: 6139-6144
  CrossrefPubMedGoogle Scholar
• 30 Masella R, Varì R, D’Archivio M, Santangelo C, Scazzocchio B, Maggiorella MT, Sernicola L, Titti F, Sanchez M, Di Mario U, Leto G, Giovannini C. Oxidised LDL modulate adipogenesis in 3T3-L1 preadipocytes by affecting the balance between cell proliferation and differentiation. FEBS Lett 2006; 580: 2421-2429
  CrossrefPubMedGoogle Scholar
• 31 Sul HS, Smas C, Mei B, Zhou L. Function of pref-1 as an inhibitor of adipocyte differentiation. Int J Obes Relat Metab Disord 2000; 24 (Suppl. 04) S15-S19
  PubMedGoogle Scholar
• 32 Zhang H, Schulz TJ, Espinoza DO, Huang TL, Emanuelli B, Kristiansen K, Tseng YH. Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis. Mol Cell Biol 2010; 30: 4224-4233
  CrossrefPubMedGoogle Scholar
• 33 Yamanouchi K, Yada E, Ishiguro N, Hosoyama T, Nishihara M. Increased adipogenicity of cells from regenerating skeletal muscle. Exp Cell Res 2006; 312: 2701-2711
  CrossrefPubMedGoogle Scholar
• 34 Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH. Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci USA 1999; 96: 2391-2395
  CrossrefPubMedGoogle Scholar
• 35 Whitelaw DC, Smith JM, Nattrass M. Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with type 2 diabetes and hypertriglyceridaemia. Diabetes Obes Metab 2002; 4: 187-194
  CrossrefPubMedGoogle Scholar
• 36 Skrha J, Sindelka G, Haas T, Hilgertova J, Justova V. Relation between hypertriacylglycerolemia and the action of insulin in type 2 diabetes mellitus. Cas Lek Cesk 1994; 133: 496-499
  PubMedGoogle Scholar