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Programmed regulation of rat offspring adipogenic transcription factor (PPARγ) by maternal nutrition*

Published online by Cambridge University Press:  19 August 2015

M. Desai
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
J. K. Jellyman
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
G. Han
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA
R. H. Lane
Affiliation:
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
M. G. Ross
Affiliation:
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Corresponding
E-mail address:

Abstract

We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARγ with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARγ with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARγ expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARγ co-regulators are necessary to establish their role in PPARγ-mediated programmed obesity.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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Footnotes

*

The work was done at the Perinatal Research Laboratories, Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

References

1. Ross, MG, Desai, M. Developmental programming of offspring obesity, adipogenesis, and appetite. Clin Obstet Gynecol. 2013; 56, 529536.Google Scholar
2. Desai, M, Ross, MG. Fetal programming of adipose tissue: effects of intrauterine growth restriction and maternal obesity/high-fat diet. Semin Reprod Med. 2011; 29, 237245.Google Scholar
3. Breton, C. The hypothalamus-adipose axis is a key target of developmental programming by maternal nutritional manipulation. J Endocrinol. 2013; 216, R19R31.Google Scholar
4. Ailhaud, G, Grimaldi, P, Négrel, R. Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr. 1992; 12, 207233.Google Scholar
5. Rosen, ED, Walkey, CJ, Puigserver, P, Spiegelman, BM. Transcriptional regulation of adipogenesis. Genes Dev. 2000; 14, 12931307.Google Scholar
6. Fajas, L, Schoonjans, K, Gelman, L, et al. Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism. Mol Cell Biol. 1999; 19, 54955503.Google Scholar
7. Kim, JB, Spiegelman, BM. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev. 1996; 10, 10961107.Google Scholar
8. Holm, C, Osterlund, T, Laurell, H, Contreras, JA. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr. 2000; 20, 365393.Google Scholar
9. Picard, F, Kurtev, M, Chung, N, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004; 429, 771776.Google Scholar
10. Feige, JN, Auwerx, J. Transcriptional coregulators in the control of energy homeostasis. Trends Cell Biol. 2007; 17, 292301.Google Scholar
11. Poissonnet, CM, Burdi, AR, Bookstein, FL. Growth and development of human adipose tissue during early gestation. Early Hum Dev. 1983; 8, 111.Google Scholar
12. Desnoyers, F. Morphological study of rat perirenal adipose tissue in the formative stage. Ann Biol Anim Biochim Biophys. 1977; 17, 787798.Google Scholar
13. Desai, M, Jellyman, JK, Han, G, et al. Rat maternal obesity and high-fat diet program offspring metabolic syndrome. Am J Obstet Gynecol. 2014; 211, 237.e1237.e13.Google Scholar
14. Desai, M, Gayle, D, Babu, J, Ross, MG. Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R91R96.Google Scholar
15. Desai, M, Guang, H, Ferelli, M, Kallichanda, N, Lane, RH. Programmed upregulation of adipogenic transcription factors in intrauterine growth-restricted offspring. Reprod Sci. 2008; 15, 785796.Google Scholar
16. Yee, JK, Lee, WN, Ross, MG, et al. Peroxisome proliferator-activated receptor gamma modulation and lipogenic response in adipocytes of small-for-gestational age offspring. Nutr Metab (Lond). 2012; 9, 62.Google Scholar
17. Yee, JK, Lee, WN, Han, G, Ross, MG, Desai, M. Organ-specific alterations in fatty acid de novo synthesis and desaturation in a rat model of programmed obesity. Lipids Health Dis. 2011; 10, 72.Google Scholar
18. Seet, EL, Yee, JK, Jellyman, JK, Han, G, Ross, MG, Desai, M. Maternal high-fat-diet programs rat offspring liver fatty acid metabolism. Lipids. 2015; 50, 565573.Google Scholar
19. Yee, JK, Lee, WN, Ross, MG, et al. Peroxisome proliferator-activated receptor gamma modulation and lipogenic response in adipocytes of small-for-gestational age offspring. Nutr Metab (Lond). 2012; 9, 62.Google Scholar
20. Cooke, PS, Naaz, A. Role of estrogens in adipocyte development and function. Exp Biol Med (Maywood). 2004; 229, 11271135.Google Scholar
21. Gast, KB, den Heijer, M, Smit, JW, et al. Individual contributions of visceral fat and total body fat to subclinical atherosclerosis: the NEO study. Atherosclerosis. 2015; 241, 547554.Google Scholar
22. Amutha, A, Ali, MK, Unnikrishnan, R, et al. Insulin sensitivity and secretion in youth onset type 2 diabetes with and without visceral adiposity. Diabetes Res Clin Pract. 2015; 109, 3239.Google Scholar
23. Umek, RM, Friedman, AD, McKnight, SL. CCAAT-enhancer binding protein: a component of a differentiation switch. Science. 1991; 251, 288292.Google Scholar
24. Freytag, SO, Paielli, DL, Gilbert, JD. Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. Genes Dev. 1994; 8, 16541663.Google Scholar
25. Wu, Z, Rosen, ED, Brun, R, et al. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999; 3, 151158.Google Scholar
26. Sztalryd, C, Kraemer, FB. Regulation of hormone-sensitive lipase during fasting. Am J Physiol. 1994; 266(2 Pt 1), E179E185.Google Scholar
27. Jocken, JW, Langin, D, Smit, E, et al. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. J Clin Endocrinol Metab. 2007; 92, 22922299.Google Scholar
28. Wang, H, Eckel, RH. Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab. 2009; 297, E271E288.Google Scholar
29. Weinstock, PH, Levak-Frank, S, Hudgins, LC, 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 USA. 1997; 94, 1026110266.Google Scholar
30. Li, P, Fan, W, Xu, J, et al. Adipocyte NCoR knockout decreases PPARγ phosphorylation and enhances PPARγ activity and insulin sensitivity. Cell. 2011; 147, 815826.Google Scholar
31. Desai, M, Gayle, D, Babu, J, Ross, MG. The timing of nutrient restriction during rat pregnancy/lactation alters metabolic syndrome phenotype. Am J Obstet Gynecol. 2007; 196, 555.e1555.e7.Google Scholar
32. Picard, F, Géhin, M, Annicotte, J, et al. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002; 111, 931941.Google Scholar
33. Louet, JF, Chopra, AR, Sagen, JV, et al. The coactivator SRC-1 is an essential coordinator of hepatic glucose production. Cell Metab. 2010; 12, 606618.Google Scholar
34. Jin, Q, Zhang, F, Yan, T, et al. C/EBPalpha regulates SIRT1 expression during adipogenesis. Cell Res. 2010; 20, 470479.Google Scholar
35. Larsen, TM, Toubro, S, Astrup, A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27, 147161.Google Scholar
36. Chui, PC, Guan, HP, Lehrke, M, Lazar, MA. PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1. J Clin Invest. 2005; 115, 22442256.Google Scholar
37. Jones, PL, Shi, YB. N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors. Curr Top Microbiol Immunol. 2003; 274, 237268.Google Scholar
38. Vidal-Puig, A, Jimenez-Liñan, M, Lowell, BB, et al. Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Invest. 1996; 97, 25532561.Google Scholar
39. Hörlein, AJ, Näär, AM, Heinzel, T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995; 377, 397404.Google Scholar
40. Yokoi, H, Mizukami, H, Nagatsu, A, Tanabe, H, Inoue, M. Hydroxy monounsaturated fatty acids as agonists for peroxisome proliferator-activated receptors. Biol Pharm Bull. 2010; 33, 854861.Google Scholar
41. Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review. Nutr J. 2014; 13, 17.Google Scholar
42. Tontonoz, P, Spiegelman, BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem. 2008; 77, 289312.Google Scholar
43. Joss-Moore, LA, Wang, Y, Campbell, MS, et al. Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity. Early Hum Dev. 2010; 86, 179185.Google Scholar
44. Janesick, A, Blumberg, B. Minireview: PPARγ as the target of obesogens. J Steroid Biochem Mol Biol. 2011; 127, 48.Google Scholar
45. Vidal-Puig, AJ, Considine, RV, Jimenez-Liñan, M, et al. Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest. 1997; 99, 24162422.Google Scholar
46. Sertie, RA, Andreotti, S, Proença, AR, et al. Cessation of physical exercise changes metabolism and modifies the adipocyte cellularity of the periepididymal white adipose tissue in rats. J Appl Physiol (1985). 2013; 115, 394402.Google Scholar
47. Sun, C, Zeng, R, Cao, G, et al.. Vibration training triggers brown adipocyte relative protein expression in rat white adipose tissue. Biomed Res Int. 2015; 2015, 919401.Google Scholar
48. Schug, TT, Li, X. Sirtuin 1 in lipid metabolism and obesity. Ann Med. 2011; 43, 198211.Google Scholar
49. Sutanto, MM, Ferguson, KK, Sakuma, H, et al.. The silencing mediator of retinoid and thyroid hormone receptors (SMRT) regulates adipose tissue accumulation and adipocyte insulin sensitivity in vivo. J Biol Chem. 2010; 285, 1848518495.Google Scholar

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