DOI QR코드

DOI QR Code

Effects of maternal undernutrition during late pregnancy on the regulatory factors involved in growth and development in ovine fetal perirenal brown adipose tissue

  • Yang, Huan (College of Animal Science, Inner Mongolia Key Laboratory of animal nutrition and feed, Inner Mongolia Agricultural University) ;
  • Ma, Chi (College of Animal Science, Inner Mongolia Key Laboratory of animal nutrition and feed, Inner Mongolia Agricultural University) ;
  • Zi, Yang (College of Animal Science, Inner Mongolia Key Laboratory of animal nutrition and feed, Inner Mongolia Agricultural University) ;
  • Zhang, Min (College of Animal Science, Inner Mongolia Key Laboratory of animal nutrition and feed, Inner Mongolia Agricultural University) ;
  • Liu, Yingchun (College of Life Science, Inner Mongolia Key Laboratory of Biomanufacturing, Inner Mongolia Agricultural University) ;
  • Wu, Kaifeng (College of Life Science, Inner Mongolia Key Laboratory of Biomanufacturing, Inner Mongolia Agricultural University) ;
  • Gao, Feng (College of Animal Science, Inner Mongolia Key Laboratory of animal nutrition and feed, Inner Mongolia Agricultural University)
  • Received : 2021.04.25
  • Accepted : 2021.08.27
  • Published : 2022.07.01

Abstract

Objective: The experiment was conducted to evaluate the effects of maternal undernutrition during late pregnancy on the expressions of genes involved in growth and development in ovine fetal perirenal brown adipose tissue (BAT). Methods: Eighteen ewes with singleton fetuses were allocated to three groups at day 90 of pregnancy: restricted group 1 (RG1, 0.33 MJ metabolisable energy [ME]/kg body weight [BW]0.75/d, n = 6), restricted group 2 (RG2, 0.18 MJ ME/kg BW0.75/d, n = 6), and a control group (CG, ad libitum, 0.67 MJ ME/kg BW0.75/d, n = 6). The fetuses were removed at day 140 of pregnancy. All data were analyzed by using the analysis of variance procedure. Results: The perirenal fat weight (p = 0.0077) and perirenal fat growth rate (p = 0.0074) were reduced in RG2 compared to CG. In fetal perirenal BAT, the protein level of uncoupling protein 1 (UCP1) (p = 0.0001) was lower in RG1 and RG2 compared with CG and UCP1 mRNA expression (p = 0.0265) was decreased in RG2. The protein level of myogenic factor 5 (Myf5) was also decreased in RG2 (p = 0.0001). In addition, mRNA expressions of CyclinA (p = 0.0109), CyclinB (p = 0.0019), CyclinD (p = 0.0015), cyclin-dependent kinase 1 (CDK1) (p = 0.0001), E2F transcription factor 1 (E2F1) (p = 0.0323), E2F4 (p = 0.0101), and E2F5 (p = 0.0018) were lower in RG1 and RG2. There were decreased protein expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p = 0.0043) and mRNA expression of CCAAT/enhancer-binding protein-α (C/EBPα) (p = 0.0307) in RG2 and decreased PPARγ mRNA expression (p = 0.0008) and C/EBPα protein expression (p = 0.0015) in both RG2 and RG1. Furthermore, mRNA expression of bone morphogenetic protein 4 (BMP4) (p = 0.0083) and BMP7 (p = 0.0330) decreased in RG2 and peroxisome proliferator-activated receptor co-activator-1α (PGC-1α) reduced in RG2 and RG1. Conclusion: Our observations support that repression of regulatory factors promoting differentiation and development results in the inhibition of BAT maturation in fetal perirenal fat during late pregnancy with maternal undernutrition.

Keywords

Acknowledgement

We gratefully acknowledge Dr. Feng-Qi Zhao (Department of Animal and Veterinary Sciences, University of Vermont, Burlington) for help with the manuscript.

References

  1. Aherne W, Hull D. Brown adipose tissue and heat production in the newborn infant. J Pathol Bacteriol 1966;91:223-34. https://doi.org/10.1002/path.1700910126
  2. Farmer SR. Molecular determinants of brown adipocyte formation and function. Genes Dev 2008;22:1269-75. https://doi.org/10.1101/gad.1681308
  3. Hansen JB, Kristiansen K. Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem J 2006; 398:153-68. https://doi.org/10.1042/BJ20060402
  4. Klingenberg M. Uncoupling protein-a useful energy dissipator. J Bioenerg Biomembr 1999;31:419-30. https://doi.org/10.1023/a:1005440221914
  5. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004;84:277-359. https://doi.org/10.1152/physrev.00015.2003
  6. Kajimura S, Saito M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol 2014;76:225-49. https://doi.org/10.1146/annurev-physiol-021113-170252
  7. Berry DC, Stenesen D, Zeve D, Graff JM. The developmental origins of adipose tissue. Development 2013;140:3939-49. https://doi.org/10.1242/dev.080549
  8. Lukaszewski MA, Eberle D, Vieau D, Breton C. Nutritional manipulations in the perinatal period program adipose tissue in offspring. Am J Physiol Endocrinol Metab 2013;305:e1195-207. https://doi.org/10.1152/ajpendo.00231.2013
  9. Wallacea JM, Milnea JS, Aitken RP, et al. Undernutrition and stage of gestation influence fetal adipose tissue gene expression. J Mol Endocrinol 2015;54:263-75. https://doi.org/10.1530/JME-15-0048
  10. Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab 2010;11:257-62. https://doi.org/10.1016/j.cmet.2010.03.005
  11. Park A, Kim WK, Bae KH. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells. World J Stem Cells 2014;6:33-42. https://doi.org/10.4252/wjsc.v6.i1.33
  12. Ali AT, Hochfeil WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013;92:229-36. https://doi.org/10.1016/j.ejcb.2013.06.001
  13. Pope M, Budge H, Symonds ME. The developmental transition of ovine adipose tissue through early life. Acta Physiol 2014;210:20-30. https://doi.org/10.1111/apha.12053
  14. Lefterova MI, Lazar MA. New developments in adipogenesis. Trends Endocrinol Metab 2009;20:107-14. https://doi.org/10.1016/j.tem.2008.11.005
  15. Satterfield MC, Dunlap KA, Bazer FW, Wu G. Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep. Amino Acids 2013;45:489-99. https://doi.org/10.1007/s00726-011-1168-8
  16. Nissen PM, Oksbjerg N. Quantification of prenatal effects on productivity in pigs. In: Greenwood PL, Bell AW, Vercoe PE, et al, editors. Managing the prenatal environment to enhance livestock productivity. New York, USA: Springer; 2010. pp. 37-70.
  17. Xu YM. Death causes and countermeasures of newborn lambs in northern cold season. Zhongguo Dongwu Baojian 2013;3:56-7.
  18. Budge H, Dandrea J, Mostyn A, et al. Differential effects of fetal number and maternal nutrition in late gestation on prolactin receptor abundance and adipose tissue development in the neonatal lamb. Pediatr Res 2003;53:302-8. https://doi.org/10.1203/01.PDR.0000047653.73271.C4
  19. Gao F, Liu YC, Zhang CZ, Zhang ZH, Song SS. Effect of intrauterine growth restriction during late pregnancy on the growth performance, blood components, immunity and anti-oxidation capability of ovine fetus. Livest Sci 2013;155:435-41. https://doi.org/10.1016/j.livsci.2013.04.016
  20. Symonds ME, Budge H, Stephenson T, McMillen IC. Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges. Reproduction 2001;121:853-62. https://doi.org/10.1530/rep.0.1210853
  21. Symonds ME, Mostyn A, Pearce S, Budge H, Stephenson T. Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol 2003;179:293-9. https://doi.org/10.1677/joe.0.1790293
  22. Tang QQ, Lane MD. Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 2012;81:715-36. https://doi.org/10.1146/annurev-biochem-052110-115718
  23. Satterfield MC, Wu G. Brown adipose tissue growth and development: significance and nutritional regulation. Front Biosci (Landmark Ed), 2011;16:1589-608. https://doi.org/10.2741/3807
  24. Lynes MD, Tseng YH. Unwiring the transcriptional heat circuit. PNAS 2014;111:14318-9. https://doi.org/10.1073/pnas.1416145111
  25. Otto TC, Lane MD. Adipose development: from stem cell to adipocyte. Cr Rev Biochem Mol Biol 2005;40:229-42. https://doi.org/10.1080/10409230591008189
  26. Johnson DG, Walker CL. Cyclins and cell cycle checkpoints. Annu Rev Pharmacol Toxicol 1999;39:295-312. https://doi.org/10.1146/annurev.pharmtox.39.1.295
  27. Barrierea C, Santamaria D, Cerqueiraa A, et al. Mice thrive without Cdk4 and Cdk2. Mol Oncol 2007;1:72-83. https://doi.org/10.1016/j.molonc.2007.03.001
  28. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci 2005;30:630-41. https://doi.org/10.1016/j.tibs.2005.09.005
  29. Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2001;2:21-32. https://doi.org/10.1038/35048096
  30. Calbo J, Parreno M, Sotillo E, et al. G1 Cyclin/cyclin-dependent kinase-coordinated phosphorylationof endogenous pocket proteins differentially regulates their interactions with E2F4 and E2F1 and gene expression. J Biol Chem 2002;277:50263-74. https://doi.org/10.1074/jbc.M209181200
  31. Lynes MD, Tseng YH. Deciphering adipose tissue heterogeneity. Ann NY Acad Sci 2018;1411:5-20. https://doi.org/10.1111/nyas.13398
  32. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006;7:885-96. https://doi.org/10.1038/nrm2066
  33. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006;4:263-73. https://doi.org/10.1016/j.cmet.2006.07.001
  34. Duffield JA, Vuocolo T, Tellam R, et al. Intrauterine growth restriction and the sex specific programming of leptin and peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA expression in visceral fat in the lamb. Pediatr Res 2009;66:59-65. https://doi.org/10.1203/PDR.0b013e3181a7c121
  35. Mota de Sa P, Richard AJ, Hang H, Stephens JM. Transcriptional regulation of adipogenesis. Compr Physiol 2017;7:635-74. https://doi.org/10.1002/cphy.c160022
  36. Seale P. Transcriptional regulatory circuits controlling brown fat development and activation. Diabetes 2015;64:2369-75. https://doi.org/10.2337/db15-0203
  37. Wang W, Kissig M, Rajakumari S, et al. Ebf2 is a selective marker of brown and beige adipogenic precursor cells. Proc Natl Acad Sci USA 2014;111:14466-71. https://doi.org/10.1073/pnas.1412685111
  38. Rajakumari S, Wu J, Ishibashi J, et al. EBF2 Determines and maintains brown adipocyte identity. Cell Metab 2013;17:562-74. https://doi.org/10.1016/j.cmet.2013.01.015
  39. Elsen M, Raschke S, Tennagels N, et al. BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells. Am J Physiol Cell Physiol 2014;306:C431-40. https://doi.org/10.1152/ajpcell.00290.2013
  40. Harris RBS. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta Mol Basis Dis 2014;1842:414-23. https://doi.org/10.1016/j.bbadis.2013.05.009
  41. Harms MJ, Ishibashi J, Wang W, et al. Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Metab 2014;19:593-604. https://doi.org/10.1016/j.cmet.2014.03.007
  42. Cheng CF, Ku HC, Lin H. PGC-1α as a pivotal factor in lipid and metabolic regulation. Int J Mol Sci 2018;19:3447. https://doi.org/10.3390/ijms19113447
  43. Tong Q, Tsai J, Hotamisligil GS. GATA transcription factors and fat cell formation. Drug News Perspec 2003;16:585-8. https://doi.org/10.1358/dnp.2003.16.9.829340
  44. Ignotz RA, Massague J. Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts. Proc Natl Acad Sci USA 1985;82:8530-4. https://doi.org/10.1073/pnas.82.24.8530