Adiponectin mRNA Levels in Parametrial Adipose Tissue and Serum Adiponectin Levels are Reduced in Mice During Late Pregnancy

Abstract

Adiponectin, a fat-derived factor, is downregulated in insulin resistance and obesity; insulin resistance has been demonstrated during late pregnancy in both humans and in rodents. The present study examines the physiological change of adiponectin gene expression as well as the circulating levels of adiponectin during pregnancy. We examined the relative quantity of adiponectin mRNA produced in the adipose tissues of pregnant compared to virgin mice. We also measured serum adiponectin levels and parametrial adipocyte size in mice throughout pregnancy. Adiponectin mRNA was significantly reduced by 74 ± 8 % and 63 ± 4 % at days 15 and 18 of pregnancy, respectively, compared to virgin mice. Serum adiponectin concentration decreased on days 15 (30.7 ± 8.5 µg/ml) and 18 (27.9 ± 8.7 µg/ml) of pregnancy, and the values were significantly lower than that of virgin mice (56.8 ± 6.6 µg/ml). Parametrial adipocytes from mice on days 15 and 18 of pregnancy were significantly larger than in virgin mice or during early pregnancy. Fat-cell size was closely correlated to degradation of adiponectin gene expression and serum adiponectin levels. These results suggest that changes of adiponectin expression affect metabolic status in pregnant mice.

Adiponectin - Adipose tissue - Pregnancy - Mice

References

• 1 Hu E, Liang P, Spiegelman B M. AdipoQ is a novel adipose-specific gene dysregulated in obesity.  J Biol Chem. 1996;  271 10 697-10 703
• 2 Friedman J M. Obesity in the new millennium.  Nature. 2000;  404 632-634
• 3 Hotamisligil G S, Shargill N S, Spiegelman B M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.  Science. 1993;  259 87-91
• 4 Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity.  Nat Med. 1996;  2 800-803
• 5 White R T, Damm D, Hancock N, Rosen B S, Lowell B B, Usher P, Flier J S, Spiegelman B M. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue.  J Biol Chem. 1992;  267 9210-9213
• 6 Steppan C M, Bailey S T, Bhat S, Brown E J, Banerjee R R, Wright C M, Patel H R, Ahima R S, Lazar M A. The hormone resistin links obesity to diabetes.  Nature. 2001;  409 307-312
• 7 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman M L, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.  Nat Med. 2001;  7 941-946
• 8 Stefan N, Stumvoll M. Adiponectin-its role in metabolism and beyond.  Horm Metab Res. 2002;  34 469-474
• 9 Yoneda M, Miyatake T, Attardi G. Complementation of mutant and wild-type human mitochondrial DNAs coexisting since the mutation event and lack of complementation of DNAs introduced separately into a cell within distinct organelles.  Mol Cell Biol. 1994;  14 2699-2712
• 10 Ryan E A, O’Sullivan M J, Skyler J S. Insulin action during pregnancy: studies with the euglycemic clamp technique.  Diabetes. 1985;  34 380-389
• 11 Leturque A, Ferre P, Burnol A F, Kande J, Maulard P, Girard J. Glucose utilization rates and insulin sensitivity in vivo in tissues of virgin and pregnant rats.  Diabetes. 1986;  35 172-177
• 12 Leturque A, Burnol A F, Ferre P, Girard J. Pregnancy-induced insulin resistance in the rat: assessment by glucose clamp technique.  Am J Physiol. 1984;  246 E25-31
• 13 Mersmann H J, MacNeil M D. Variables in estimation of adipocyte size and number with a particle counter.  J Anim Sci. 1986;  62 980-991
• 14 Sohlstrom A, Petterson U, Forsum E. Triglyceride turnover, lipoprotein lipase activity, and fat cell size in adipose tissue of rats during the first 2 weeks of pregnancy.  Ann Nutr Metab. 1998;  42 55-62
• 15 Bernbaum M, Albert S G, Miller D, Stich T, Hoffmann J W, Mooradian A D. Effectiveness of glucose monitoring systems modified for the visually impaired.  Diabetes Care. 1993;  16 1363-1366
• 16 Combs T P, Berg A H, Rajala M W, Klebanov S, Iyengar P, Jimenez-Chillaron J C, Patti M E, Klein S L, Weinstein R S, Scherer P E. Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin.  Diabetes. 2003;  52 268-76
• 17 Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese zucker rats.  J Clin Invest. 1998;  101 1354-1361
• 18 Savard R, Greenwood M R. Site specificity of fat cell lipolysis during pregnancy in two strains of rats.  Can J Physiol Pharmacol. 1993;  71 234-240
• 19 Andersen O, Kuhl C. Adipocyte insulin receptor binding and lipogenesis at term in normal pregnancy.  Eur J Clin Invest. 1998;  18 575-581
• 20 Leturque A, Guerre-Millo M, Lavau M, Girard J. Effect of insulin on glucose metabolism in adipocytes from virgin and late-pregnant rats.  Biochem J. 1984;  224 685-688
• 21 Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes.  Biochem Biophys Res Commun. 2002;  290 1084-1089
• 22 Mohlig M, Wegewitz U, Osterhoff M, Isken F, Ristow M, Pfeiffer A FH, Spranger J. Insulin decreases human adiponectin plasma levels.  Horm Metab Res. 2002;  34 655-658